Atlas of

Parasitic Pathology
 Dedicated to
Prof. H. M . Seitz, M D and Prof. U. Pfeifer, M D ,
University of B o n n , Germany,
w h o s e help in c o m p l e t i n g this atlas is very m u c h appreciated
Current Histopathology
Consultant Editor
Professor G. Austin Gresham, TD, ScD, M D , FRCPath.
Professor of Morbid Anatomy and Histology, University of Cambridge

Volume Twenty

PARASITIC
PATHOLOGY
By
K. S A L F E L D E R
Prof. Titular
Laboratorio de Investigacion en Patologia
Facultad de M e d i c i n a
Universidad de Los A n d e s , Merida,
Venezuela S A

Assisted by
T. R. de Liscano
Prof. Titular
and

E. Sauerteig
Profesor Asesor
Laboratorio de Investigacion en Patologia
Facultad de M e d i c i n a
Universidad de Los A n d e s , Merida
Venezuela S A

SPRINGER SCIENCE+BUSINESS MEDIA, B.V.

 A catalogue record for this book is available from the
British Library.
ISBN 978-94-010-4988-7

Library of C o n g r e s s C a t a l o g i n g in P u b l i c a t i o n
Data

Salfelder, Karlhanns, 1 9 1 9 -
Copyright Atlas of parasitic pathology / by K. Salfelder ;
assisted by T.R. de L i s c a n o and E. Sauerteig,
© 1 9 9 2 by S p r i n g e r S c i e n c e + B u s i n e s s M e d i a D o r d r e c h t
p. c m . — (Current h i s t o p a t h o l o g y ; v. 20)
O r i g i n a l l y p u b l i s h e d by K l u w e r A c a d e m i c P u b l i s h e r s in
Includes biblioaraphical references and index.
1992
ISBN 978-94-010-4988-7 ISBN 978-94-011-2228-3 (eBook)
A l l rights reserved. N o part of this publication may be DOI 1 0 . 1 0 0 7 / 9 7 8 - 9 4 - 0 1 1 - 2 2 2 8 - 3
r e p r o d u c e d , stored in a retrieval system, or transmitted
1. Parasitic diseases — Atlases. 2. Parasitic
in any form or by any means, electronic, m e c h a n i c a l ,
d i s e a s e s — H i s t o p a t h o l o g y — Atlases. I. L i s c a n o ,
p h o t o c o p y i n g , recording or otherwise, w i t h o u t prior
T. R. de. II. Sauerteig, Eberhard. III. Title.
permission from the publishers, Kluwer A c a d e m i c
IV. Series.
Publishers B V , P O B o x 17, 3 3 0 0 A A Dordrecht, The
[ D N L M : 1. Parasitic Diseases — p a t h o l o g y —
Netherlands.
atlases. W1 C U 7 8 8 J B A v. 20 / W C 17 S 1 6 3 a c ]
RC119.S24 1992
616.9'607 — dc20
DNLM/DLC
for Library of C o n g r e s s 92-49790
CIP
Contents

Consultant editor's note 7 26 Toxocariasis 115

27 Anisakiasis 115
Preface 8 28 G nathostom iasis 117
29 Angiostrongylosis 119
Parasitic diseases 9 30 Capillariasis 124
31 Dracunculosis 124
II Protozoan diseases 13
Filaria infections 126
Haemoflagellate infections 13 32 Filariasis 126
1 American trypanosomiasis 13 33 Loiasis 128
2 African trypanosomiasis 23 34 Onchocerciasis 131
Leishmaniases 26 35 Dirofilariasis 135
3 Cutaneous leishmaniasis 27 36 Rare and uncommon nematodiases 137
4 Mucocutaneous leishmaniasis 27 37 Larva migrans 138
5 Visceral leishmaniasis 35
B. Cestodiasis 141
6 Giardiasis 39 38 Taeniasis 141
7 T richomon iasis 41 39 Diphyllobothriasis 143
8 Amoebiasis 43 40 Dipylidiasis 145
9 Acanthamoebiasis 49 41 Hymenolepiasis 145
10 Blastocystis infection 56 42 Cysticercosis 147
11 Toxoplasmosis 59 43 Echinococcosis 148
12 Babesiosis 69
13 Sarcosporidiosis 72 C. Trematodiasis 151
14 Isosporosis 73 44 Blood fluke infection 151
15 Cryptosporidiosis 76 45 Lung trematode infection 160
16 Malaria 77 46 Liver trematode infection 163
17 Pneumocystosis 85 47 Intestinal fluke infections 169
18 Balantidiasis 91
19 M icrosporidiosis 94 D. Worm eggs 171

III Helminthic diseases 96 IV Disorders caused by arthropods 173

A. Nematodiasis 96 48 Scabies 173
20 Enterobiasis 97 49 Demodicidosis 175
21 Ascariasis 100 50 Tungiasis 178
22 Trichuriasis 101 51 Myiasis 181
23 Uncinariasis 106 52 Pentastomiasis 184
24 Strongyloidiasis 109
25 Trichinosis 112 Index 186

5
Current Histopathology Series

Already published in this series:

Volume 1 Atlas of Lymph Node Pathology
Volume 2 Atlas of Renal Pathology
Volume 3 Atlas of Pulmonary Pathology
Volume 4 Atlas of Liver Pathology
Volume 5 Atlas of Gynaecological Pathology
Volume 6 Atlas of Gastrointestinal Pathology
Volume 7 Atlas of Breast Pathology
Volume 8 Atlas of Oral Pathology
Volume 9 Atlas of Skeletal Muscle Pathology
Volume 10 Atlas of Male Reproductive Pathology
Volume 11 Atlas of Skin Pathology
Volume 12 Atlas of Cardiovascular Pathology
Volume 13 Atlas of Experimental Toxicological Pathology
Volume 14 Atlas of Serous Fluid Cytopathology
Volume 15 Atlas of Bone Marrow Pathology
Volume 16 Atlas of Ear. Nose and Throat Pathology
Volume 17 Atlas of Fungal Pathology
Volume 18 Atlas of Synovial Fluid Cytopathology
Volume 19 Tumours of the Mediastinum

Other volumes currently scheduled in this series include

the fol/owing titles

Atlas of AI DS Pathology

Atlas of Bone Tumours

Atlas of Neuropathology

Atlas of Endocrine Pathology

Atlas of Ocular Pathology

Atlas of Renal Transplantation Pathology

Atlas of Soft Tissue Pathology

Biopsy of Bone in Internal Medicine

Paediatric Neoplasia
Consultant Editor's Note
At the present time books on morbid anatomy and
histopathology can be divided into two broad groups:
extensive textbooks often written primarily for students
and monographs on research topics.
This takes no account of the fact that the vast majority
of pathologists are involved in an essentially practical field
of general diagnostic pathology providing an important
service to their clinical colleagues. Many of these pathol-
ogist are expected to cover a broad range of disciplines
and even those who remain solely within the field of
histopathology usually have single and sole responsibility
within the hospital for all this work. They may often have
no colleagues in the same department. In the field of
histopathology, no less than in other medical fields, there
have been extensive and recent advances, not only in
new histochemical techniques but also in the type of
specimen provided by new surgical procedures.
There is a great need for the provision of appropriate
information for this group. This need has been defined in
the following terms:
1. It should be aimed at the general clinical pathologist
7
or histopathologist with existing practical training, but
should have value for the trainee pathologist.
2. It should concentrate on the practical aspects of
histopathology taking account of the new techniques
which should be within the compass of the worker in
a unit with reasonable facilities.
3. New types of material, e.g. those derived from endo-
scopic biopsy should be covered fully.
4. There should be an adequate number of illustrations
on each subject to demonstrate the variation in appear-
ance that is encountered.
5. Colour illustrations should be used wherever they aid
recognition.
From time to time histopathologists encounter objects in
histological preparations and in cytological smears that
may be of parasitic origin. This book is a comprehensive,
well illustrated aid to such diagnostic problems.
G. A. Gresham
Preface
One large chapter of this atlas is, in some ways, a second,
enlarged and improved, edition of an atlas published some
years ago 1. The Atlas of Parasitic Pathology concentrates
intentionally on the main features of gross pathology and
the histopathology of these diseases.
I n the four subchapters of each section on a particular
parasite, the text is always arranged in the same order
(Introduction, The Parasite, Pathogenesis and Pathol-
ogy); thus, information can easily be found by the reader.
Under 'Introduction', general data are summarized in a
few sentences. Under 'Pathology', organ involvement
gross pathology and morphology ofthe aetiological agent
are followed by tissue reaction and differential diagnosis.
Several unpublished data and illustrations, as well as
personal observations and ideas, are included because
we have not published in journals for the last 15 years.
History, epidemiology, clinical data, therapy etc. are
not included. Medical students may find these details in
the 10th volume of the GKM2.
In another atlas in this series, differential diagnosis of
micro-organisms and non-living structures in tissues has
been focused on extensively3. For this reason, differential
diagnosis of parasites will be discussed here only briefly.
Since the technical terms will be explained in the text
or in footnotes, a glossary was considered superfluous.
This atlas is directed to pathologists and should be
used as a bench manual to be kept near their microscopes
for immediate consultation. Obviously, physicians and
ACKNOWLEDGEMENTS
I am very grateful to many of my colleagues and friend-
swho gave me material and photographs to illustrate
this atlas. Thanks go first to my friends in Merida and
Venezuela: R. Alvarado, A. D. de Arriaga, K. Brass, E.
Carrero, W. Diaz, R. Hernandez Perez, A. L. C. de Tirado,
G. Volcan and R. Zabala. My good friends, H. D. Eberhard,
M. Okudaira, P. Ravisse, S. Stefanko, C. Thomas, H.
Werner, and others have helped in many ways. Professor
G. Piekarski of Bonn was kind enough to give permission
to use some of his plates of the developmental cycles of
parasites.
As always, Oswaldo Juergenson, Merida was an invalu-
able help with photography.
The publishers, Oscar Todtmann, C. A. Caracas/Vene-
zuela, Schattauer-Verlag, Stuttgart FRG and Schwer-
Verlag, Stuttgart FRG, have permitted us to reproduce
previously published illustrations. We would like to
express our special gratitude to them.
The CONICIT (Consejo Nacional de Investigaciones
Cientificas y Tecnol6gicas) in Caracas and the CDCHT
8
professionals of all natural and paramedical sciences, as
well as teachers at all levels, may find it useful.
The first main chapter (I) deals with parasitic diseases
in general, and definitions of parasites and parasitic
infections. Also, data on hosts and transmission are
summarized. The principal characteristics of parasitic
disorders, in contrast to other infectious diseases, and all
the important pathogenic parasites for men, are listed.
The important parasitoses in immunodeficient patients
are mentioned.
In the following three main chapters (II-IV), protozoan
and helminthic diseases, as well as disorders caused by
arthropods, are discussed and illustrated.
Principal worm eggs and arthropods are illustrated.
Schematic drawings facilitate the understanding of the
life-cycle and evolutional stages of parasites, the portal
of entry and pathogenesis.
References
1. In Spanish: Salfelder, K. (1985). Las Protozoonosis en el Hombre.
Oscar Todtmann, C. A. Caracas/Venezuela, and in English: Salfelder,
K. (1987). Protozoan Infections in Man. Schwer-Verlag, Stuttgart/
FRG
2. Thomas. C. (1990). Grundlagen der Klinischen Medizin. Schattauer-
Verlag. Stuttgart/FRG
3. Salfelder. K. (1990). Atlas of Fungal Pathology. Vol. 17, Current
Histopathology. Kluwer Academic Publishers, Lancaster
(Consejo de Desarollo Cientifico, Humanistico y Tecno-
16gico) of the University of the Andes, Merida/Venezuela
have subsidized several research projects of the authors.
partially related to this atlas.
The academic Vice-rector of our University, Prof. Carlos
Guillermo Cardenas MD, helped us to finish this atlas.
The ex-rector, Prof. Pedro Rinc6n Gutierrez MD, founded
our laboratory and gave us support in many ways.
The DAAD (Deutscher Akademischer Austauschdienst)
of the FRG helped indirectly to finish both atlases in this
series written by us.
Professor H. M. Seitz MD and Professor U. Pfeifer MD
from Bonn, Germany assisted, in several ways. the final
phases of the drafting of this atlas and therefore it is
dedicated to these good friends.
Professor G. Austin Gresham of Cambridge. UK was
kind enough to help with the 'German' English. Thank
you, indeed. Professor Gresham.
Last but not least co-operation with Phil Johnstone.
the editor of this atlas. was superb.
Parasitic Diseases
A parasite in biology is defined in the Webster Dictionary
of 1983 as a plant or animal that lives on or within another
organism from which it derives sustenance or protection
without making compensation.
I n the Encyclopaedia Britannica, 1962 edition, parasites
are considered as organisms which live for all or part of
their lives on (ecto-) or in (endoparasites) another living
organism (host) from which they derive some benefit.
such as food, shelter or protection. Parasites producing
damage to the host are referred to as pathogens, and the
condition resulting from this damage constitutes disease.
Summarizing, there are obligatory and facultative
pathogenic parasites, temporary and stationary, as well
as endo- and ectoparasites.
I n a broad sense, parasitic diseases, or parasitoses, are
produced by any micro-organism (or macro-organism),
but conventionally in medicine, they are morbid states
due to infection with the animal parasite groups, protozoa
and helminths. The unicellular protozoa belong to the
protists of the second kingdom, and the helminths belong
to the pluricellular metazoa, of the fifth kingdom of the
living organisms. We would like to add a third group,
arthropods, which also belong to the fifth kingdom of
living organisms, since the disorders produced by these
organisms, and their role as vectors, are of interest in
medicine, especially for pathologists.
Parasitoses must be differentiated from zoonoses. The
World Health Organization (WHO) defines the zoonoses
as: diseases and infections transmitted in a natural way
between vertebrates and men. Toxoplasmosis is one of
the zoonoses. Anthropozoonoses and zooanthroponoses
are infectious diseases, whose agents are pathogens for
men and lower animals, but they differ in their mode of
infection.
Disorders caused by parasites are both of general
importance and great interest. More than one billion
human beings are infested; numerous individuals are
considerably affected and die l - 29 .
HOSTS
A dead-end host is a host in which the parasite reaches
an end point and is unable to continue its life cycle.
A principal dead-end host, or typical host, is a
host in which the parasite is commonly found and in
which the parasite can complete its development (or the
appropriate phase of its development for subsequent
completion of its life cycle).
An accessory or secondary dead-end host is one
which harbours parasites only occasionally.
An accidental host is one in which the parasite is not
commonly found; nevertheless, it is suitable for the
parasite's development. In some instances (e.g.
cysticercosis), the accidental host is a dead-end one
because, even though the parasite develops through its
9
I
Infection with parasites does not always cause disease.
Serological tests may be positive in apparently healthy
persons, often confirming that infection occurred a long
time ago.
Parasitic infections with serious disease are especially
frequent in underdeveloped countries, as well as in
tropical and subtropical regions.
Recently, these diseases have become more important
all over the world because they are observed with increas-
ing frequency as complications of diseases due to
acquired immunologic deficiencies. In this context, toxo-
plasmosis and pneumocystosis must be mentioned.
Some infections of this kind may show exacerbation and
also a more severe course in debilitated or immuno-
deficient persons than under normal conditions. This
occurs in amoebiasis, giardiasis, strongyloidiosis and
cryptosporid iosis.
Nowadays, campaigns of eradication of vectors are not
performed so regularly and systematically as in former
times, partly because many people are concerned,
excessively and fanatically, with biological equilibrium.
This neglect has caused a recrudescence of infectious
diseases which had almost been forgotten, for example
malaria, Chagas disease, sleeping disease and leishman-
iasis.
Monoxenous parasites occur only in one species, man
or one of the lower animals. Heteroxenous parasites, on
the other hand, may develop in man and lower animals.
Specific parasitoses (e.g. Taeniasis solium) occur only
in one host; non-specific parasitoses (e.g. blood-sucking
arthropods) may occur in several dead-end hosts. The
parasitic specificity may refer also to the intermediate
host.
Recommended texts on parasitology can be found in
alphabetical order in the references at the end of this
chapter.
appropriate stages, it fails to find a portal of exit, and thus
the life cycle is blocked.
An aberrant host is one in which the parasite cannot
complete its development or the appropriate phase of its
development.
A false host is a person (man) who harbours a parasite
which is usually found only in a determined lower animal
species. The parasite cannot leave or reach maturity in
this host.
A reservoir host is any host (a lower animal or
man) in which the parasite remains and is available for
transmission to another susceptible host. i.e. it is a
constant source of transmission.
10 PARASITIC DISEASES

Table 1 The principal pathogenic parasites in man

Causative agents Transmission Disease

Protozoa
Mastigophora
Trypanosoma cruzi Triatoma spp. American trypanosomias
Diaplacental Chagas disease
Trypanosoma brucei gamb. Glossina spp. African trypanosomiasis
T.brucei rhodesiense Sleeping sickness
Leishmania tropica major and minor Phlebotomus spp. Cutaneous leishmaniasis
Oriental sore
Leishmania braziliensis Lutzomyia spp. Mucocutaneous leishmaniasis
Leishmania donovani Phlebotomus spp. Visceral leishmaniasis
Lutzomyia spp. Kala-azar
Giardia lamblia oral Giardiasis
Trichomonas vaginalis direct Trichomoniasis

Rhizopoda
Entamoeba histolytica oral Amoebiasis
Naegleria fowleri transnasal Primary meningoencephalitis
Acanthamoeba castellani. A. culbertsoni. A. polyphaga transnasal Granulomatous encephalitis
Blastocystis hominis oral Blastocystis infection

Sporozoa
Toxoplasma gondii oral. diaplacental. blood transfusion Toxoplasmosis
Babesia microti. B. bovis Ixodes Babesiosis
Sarcocystis suihominis. S. bovihominis oral Sarcosporidiosis
Isospora belli oral Isosporosis
Cryptosporidium spp. oral Cryptosporidiosis
Plasmodium falciparum. P. vivax. P. ovale. P. malariae Anopheles spp. Malaria
Pneumocystis carinii inhalation Pneumocystosis

Ciliophora
Balantidium coli oral Balantidiasis

Cnidosporidia
Nosema connori etc. oral(?) Microsporidiosis

Helminths
Nematodes
Enterobius vermicularis oral Enterobiasis. oxyuriasis
Ascaris lumbricoides oral Ascariasis
Trichuria trichiura oral Trichuriasis
Ancylostoma duodenale transcutaneous Uncinariasis
Necator americanus transcutaneous
Strongyloides stercoralis transcutaneous Strongyloidiasis
Trichinella spiralis oral Trichinosis
Toxocara canis. T. cati oral Toxocariasis
Anjsacis marina oral Anisakiasis
Gnathostoma spinigerum oral Gnathostomiasis
Angiostrongylus cantonensis oral Angiostrongylosis
Angiostrongylus costaricensis oral Angiostrongylosis
Capillaria hepatica or?1 Capillariasis
Capillaria philippinensis oral Capillariasis
Dracunculus medinensis Chrysops spp. Dracunculosis
Filariae
Wuchereria bancrofti Anopheles spp. Filariasis
Brugia malayi. B. timori Culex. Aedes Elephantiasis
Loa loa Chrysops spp. Loiasis
Onchocerca volvulus Simulium spp. Onchocerciasis
Dirofilaria spp. Anopheles. Culex Dirofilariasis

Cestodes
Taenia saginata oral Taeniasis sag.
Taenia solium oral Taeniasis solium
Diphyllobothrium latum oral Diphyllobothriasis
Dipylidium caninum oral Dipylidiasis
Hymenolepsis nana oral Hymenolepiasis
Cysticercus cellulosae oral Cysticercosis
Echinococcus alveolaris. E. granulosus (hydatidosis) oral Echinococcosis

Trematodes
Schistosoma haematobium. S. mansoni. S. japonicum. S. mekongi transcutaneous Schistosomiasis. bilharziasis
Paragonimus westermani. P. africanus. P. kellicottii oral Lung fluke
Fasciola hepatica. Clonorchis sinensis. Opisthorchis felineus oral Liver fluke
Fasciolepsis buski . oral Intestinal fluke
PARASITIC DISEASES 11

Table 2 The principal arthropods

Scientific denomination Common name Diseases caused or transmitted

Pulex irritans, Ctenocephalides canis, C. felis, Fleas' Pulicosis

Tunga penetrans Chigoe flea. jigger Tungiasis
Cimex lecrularis, C hemipterus, Triatoma spp. Bugs' Cimicosis
Chagas disease
Pediculus corporis, P. capitis, P. vestimentorum, Lice' Pedicu losis
Phthirius pubis Phthiriasis
Trombicula aurumnalis, T. irritans Harvest mite, red bug, chiggers' Itch
Sarcoptes scabiei Itch mites' Scabies. scratch. eczema (psora)
Demodex folliculorum, D. brevis Pimple mites Demodicidosis of hair follicles or sebacious glands
Ixodida spp. Hard ticks Ixodiasis. acariasis. babesiosis and other infectious
diseases
Diptera (order of insects)
Anopheles, Aedes, Culex Mosquitoes or gnats' Numerous infectious diseases, e.g. malaria and
yellow fever
Simulium spp. Black flies' Onchocerciasis, Tularaemia etc.
Phlebotomus Spp" Lutzomvia spp. Sand flies' Leishmaniases, Oroya fever
Chrysops spp., Tabanus spp. Tabanid flies' Chrysosis, Loaloa
Glossina palpalis, G. morsitans Tsetse fl ies' Sleeping sickness
Musca domestica. House fly Numerous infectious diseases
Cordvlobia anthropophaga, African tumbu fly
Dermatobia hominis etc . Tropical warble fly Myiasis

• = Blood sucking

TRANSMISSION
Transmission without an intermediate host may
occur:
1. Directly person to person (e.g. Trichomonas by sexual
intercourse)
2. Through the oral portal of entry (ova or larvae).
3. Transcutaneously by contact with soil harbouring
infectious larvae.
Transmission with an intermediate host may occur:
4. Parasites may cause severe foreign body reactions and
may, by virtue of their size, obstruct hollow organs.
5. Tissue reaction due to parasites, generally, is slow,
mild and scarce. Often eosinophilic infiltrations are
present. Granulomatous reactions are usually absent.
7. Parasites, and above all protozoans, do not usually
stain histologically with special methods, as, for
instance, fungi. An exception is the PAS-positivity of
amoebae.

1. By eating raw meat or fish.
2. Through the bites or stings of insects.
In transport hosts, parasites do not reproduce, but may
go through developmental stages.
In true or biological vectors, transmission is
mechanical and a parasitic cycle with multiplication may
occur before the parasite is infective to the recipient
individual.
Parasitic diseases show certain special features
which do not occur commonly in bacterial, viral or mycotic
infections:
1. Parasites, in general, are living, but they may remain
dead in man for a long time. Certain helminths may
act as co-carcinogens. The classical locations of these
carcinomas are the bladder and the liver. Parasites may
go through a complex cycle of evolution in which
other living organisms may participate as vectors or as
temporary or terminal hosts. The variable phases of
evolution and life cycle stages may lead to very
different disease patterns.
2. The portal of entry of parasites is usually the skin or
the digestive tract, in contrast to fungi causing deep
mycoses, which are mostly inhaled.
3. Geographic and socioeconomic factors play
important role in parasitic infections.
8. Toxicity of parasites is usually lower than that of
bacteria. Allergic reactions are less frequent and less
severe in parasitic diseases, with a few exceptions
(Ascaris, Echinococcus).
9. Parasites may cause diminished absorption of food
materials and may produce heavy losses of blood or
other liquids from the gut.
References
1. Ash, L. R. and Orihel, T. C. (1980). Atlas of Human ParasitologV.
American Society of Clinical Pathologists
2. Boch, J. and Supperer, R. (1983). Veterinaermedizinische Parasito-
logie. 3. Auf!. Paul Parey Verlag
3. Brandis, H. and Otte, H. (1984). Lehrbuch der medizinischen
Mikrobiologie. 5. Auf!. Gustav Fischer Verlag
4. Desowitz, R. S. (1980). Ova and Parasites. Harper and Row
5. Diaz-Ungria, C. (1960). Parasitologfa Venezolana. Vol. 1. Segunda
parte. Protozoos en Venezuela. Parasitologia y Clinica. Editorial
Sucre, Caracas
6. Faust, E. c., Russell. P. F. and Jung, R. C. (1974). Craig V Faust,
Parasitologfa Clfnica. Versi6n espanola de la 8° edici6n en ingles.
Salvat Editores, SA Barcelona
7. Granz, W. and Ziegler, K. (1976). Tropenkrankheiten. Joh. Ambro-
sius Barth
8. Gsell, O. (1980). Importierte Infektionskrankheiten. Epidemiologie
und Therapie. Georg Thieme Verlag
9. Gutierrez, Y. (1990). Diagnostic PathologV of Parasitic Infections
an with Clinical Correlations. Lea & Febiger
10. Harms, Go, Zwingenberger, K. and Bienzle, U. (1987). AIDS in
12
Africa: Current Knowledge. Landesinstitut fuerTropenmedizin Berlin
11. Paul D. Hoeprich (ed.) (1983). Infectious Diseases, 3rd edn. Harper
and Row
12. Katz, M .. Despommier. D. D. and Gwadz, R. W (1982). Parasitic
Diseases. Springer Verlag
13. Kudo, R. R. (1966). Protozoology, 5th edn. Charles C. Thomas,
Springfield, III
14. Mandell, G. L., Douglas Jr., R. G. and Bennett. J. E. (1990).
Principles and Practice of Infectious Diseases, 3rd edn. Churchill
Livingstone
15. Mehlhorn, H. and Peters, W. (1983). Diagnose der Parasiten beim
Menschen. Gustav Fischer Verlag
16. Mehlhorn, H. and Piekarski, G. (1981). Grundriss der Parasiten-
kunde. Gustav Fischer Verlag
17. Muller, R. (1975). Worms and Disease. William Heinemann Medical
Books Limited
18. Mumcuoglu, Y. and Rufli, Th. (1982). Dermatologische Entomolo-
gie. Perimed Fachbuch Verlagsgesellschaft
19. Nauck, E. G. (1975). Lehrbuch der Tropenkrankheiten. Mohr, W,
Schuhmacher, H. H. and Weyer, F. (eds.) 4 Auf!. Georg Thieme
Verlag
PARASITIC DISEASES
20. Marcial-Rojas, R. A. (ed.) (1971). Pathology of Protozoal and
Helminthic Diseases. The Williams and Wilkins Company
21. Binford, C. H. and Connor, D. H. (eds) (1976) Pathology of
Tropical and Extraordinary Diseases, Vol. I. Armed Forces Institute
of Pathology, Washington. D.C.
22. Peters, Wand Gilles, H. M. (1977). A Colour Atlas of Tropical
Medicine and Parasitology. Wolfe Medical Publications
23. Piekarski, G. (1989). Medical Parasitology. Translation of Medizin-
ische Parasitologie in Tafeln, 3. Auflage. Springer Verlag
24. Pifano, F. (1964). Aspectos de Medicina Tropical en Venezuela.
OBE. UCV .. Caracas
25. Tischler, W (1982) Grundriss der Humanparasitologie, 3. Auf!.
Gustav Fischer Verlag
26. Spencer, H. (ed.) (1973). Tropical Pathology. Handb. Spez. Path.
Anal. Bd. 8, Springer Verlag
27. Warren, K. S. and Mahmoud, A. A. (1985). Tropical and Geograph-
ical Medicine. McGraw-Hili Book Company
28. Westphal, A. (1977). Zoologla Especial. Protozoos. Ediclones
Omega, SA Barcelona
29. Whittaker, R. H. (1969). New concepts of kingdoms of organisms.
Science, 163, 1 50
Protozoan Diseases
Protozoans are unicellular parasites. Several protozoans.
e.g. Giardia lamblia, Trichomonas vaginalis, Blastocystis
hominis and Cryptosporidium spp .. are present in the
HAEMOFLAGELLATE INFECTIONS
Trypanosomiasis and leishmaniasis infections are caused
by organisms with flagella only in the blood.
The trypanosomiases as autochthonous infections
occur in geographically limited regions where causative
agents and vectors live side by side. In man. the trypano-
somes produce two distinct diseases: the American try-
panosomiasis (Chagas disease) and the African trypano-
somiasis (sleeping disease). Only in Chagas disease are
1. AMERICAN TRYPANOSOMIASIS
Introduction
This is an important protozoan infection. also called
Chagas disease. which affects millions of people in Central
and South America 1 . It is geographically limited. Chagas
disease is endemic in Venezuela and new infections are
coming to li~ht b~cause the vectors have not been totally
eradlcated 2- . DUring the sixties. new infections were not
seen. Autochthonous infections are not found outside the
Americas.
Dogs and rodents are reservoir hosts as well as man.
More organs are involved in experimentally infected mice
than in natural infections in man (Figs. 1.1 and 1.2)
The acute form occurs mainly in children. Often the
infection is asymptomatic. or there are many clinical
symptoms which depend in each case on the organ or
organ system involved Rarely is an early diagnosis made.
In symptomatic cases. the prognosis is bad. The chronic
form is observed mostly in older people and chronic
myocarditis is one of the most frequent causes of sudden
death. Chronic T cruzi infections. however. do not appear
to be a public health problem in Venezuela atthe momentS
Clinical aetiologic diagnosis is not easy. The causative
agent should be demonstrated. I n the acute form. trypo-
mastigotes should be looked for in the blood; this is done
with good results at the University Hospital in Barinas.
The search for amastigotes in muscle biopsies may be
successful (Fig. 1.3). In the chronic form. xenodiagnosis*
may be positive, or the infection may be proved only by
serological methods. The indirect immunofluorescent
procedure has been developed recently for detecting intact
amastigotes and phagocytosed amorphous antigen. both
intensely fluorescent in human and mouse myocardia 9 .
'Xenodiagnosis is the confirmation of a causative agent in a (human)
patient through the development of the parasite in a non-vertebrate
(vector) which has been exposed to the patient. For example. promasti-
gotes of T cruzi are observed in a previously healthy triatomid after it
has sucked blood from a patient with Chagas disease.
13
II
lumens of hollow organs without invasion of tissues. Only
a few of the numerous protozoan species are pathogenic
for man.
amastigotes found, i.e. parasites without flagella, also
called leishmanial forms, in the tissues of man and lower
animals. Leishmaniasis, exists in man in three forms: the
cutaneous. the mucocutaneous and the visceral forms.
The leishmanias in the three forms are morphologically
identical in tissues and structurally resemble amastigotes
of Trypanosoma cruzi.
The parasite
The genus Trypanosoma belongs to the family Trypano-
somatidae. The species Trypanosoma cruzi seems to
be the only causative agent of Chagas disease. Lately,
Trypanosoma rangeli has been discussed as a causative
agent too. Numerous people in Venezuela. Colombia and
Panama are infected with this other species. However,
the parasites have been found only in the blood of man
and not in tissues.
The trypomastigote (flagellate form) of T cruzi in the
blood is 3 Jim wide and 16~22 Jim long including the
flagellum. In fixed smears, it is seen as a (C) or (U) form
(Fig. 1.4). Its nucleus is situated in the centre of the
parasite, is oval-shaped and stains reddish pink with
Giemsa. The kinetoplast. 1 Jim in diameter. is prominent
and located in the pointed rear part. It represents a
particular form of mitochondria. Near the kinetoplast is
the base of the flagellum, called the blepharoplast This
structure cannot be differentiated under a light micro-
scope but it is possible with an electron microscope. The
trypomastigotes do not multiply in blood. T rangeli shows
only minimal structural differences when compared with
T cruzi (Fig 1.5). The flagellum in the latter is shorter.
Furthermore, both species may be differentiated by their
sialic acid content 10
After penetrating the tissue cells, the flagellum cannot
be discerned with the light microscope within the cell. The
parasite transforms into an amastigote with a rudimentary
flagellum visible only under an electron microscope.
Under the light microscope. these amastigotes, without
flagella, reveal a peripherally localized nucleus, measuring
3~5 Jim in diameter and are arranged in nests or pseudo-
cysts, mostly in muscle and glial cells (Figs. 1.6 and 1.7).
These pseudocysts do not have an individual capsule.
The amastigotes contain, in addition to the nucleus, a
characteristic rod-like kinetoplast. generally darker than
the nucleus in the H&E and Giemsa stain. The amastigotes
of T cruzi are called also 'Ieishmanial forms'. Parasites in
the amastigote form are also found in tissue culture.
14 PROTOZOAN DISEASES

Fig.1.1 Nest of amastigotes of Trypanosoma cruzi in the mycoardium Fig.1.2 Nest of amastigotes of Trypanosoma cruzi in the mediastinal
of a mouse inoculated intraperitoneally with the excrement of parasitized fat tissue of the same mouse as in Fig. 1.1. H&E
vector bugs. H&E

Fig.1.3 Amastigote nest of Trypanosoma cruzi in the muscular fibres Fig. 1.4 Trypomastigote of Trypanosoma cruzi in a blood smear.
of a human tongue. H&E Giemsa

.-

- ..

..
Fig. 1.5 Trypomastigote of Trypanosoma rangeli in a blood smear. Fig.1.6 Nest of amastigotes (parasites without flagellum) of Trvpano-
Giemsa soma cruzi in a muscle fibre of myocardium. H&E
PROTOZOAN DISEASES
Trypanosoma cruzi may be isolated from human and
animal blood relatively easily, as well as from the intestinal
tract of the vectors in the culture medium known as N NN
(for composition, see the section on Visceral Leishman-
iasis). In the culture media, the trypomastigotes of T. cruzi
are called epimastigotes and are often arranged in a rosette
pattern. If preservation of live strains of trypanosomes for
a longer period is planned, it is necessary to include
intermediate steps in animals and subcultures.
Numerous species of mammals are reservoirs of T. cruzi,
including, among others, marsupials, bats, rodents, dogs,
cats, pigs and monkeys.
Regarding the vectors, 66 species of the genus Tri-
atoma, bugs of the family Reduviidae, have been found
to be naturally infected with T. cruzi (Fig. 1.8). Their
habitat extends from sea level to an altitude of 800-
1200 m. They are found predominantly in the thatched
roofs of rural houses.
Pathogenesis
In the acute form of the infection, pathogenesis is easy
to understand. Transmission of T. cruzi occurs from man
to man or animal to man through defecation after the
insect bite, more rarely through blood transfusions or,
occasionally, diaplacentally. By contrast. transmission of
T. rangeli takes place directly through an insect bite and
not via evacuation. ' numerous books. However, in experimentally infected
The metacyclic trypomastigotes, the infectious forms
of T. cruzi which develop from the epimastigotes in the
insect gut contents, enter the host through damaged
mucosa or skin. At the conjunctiva, the so-called 'Romana
sign' may be observed (Fig. 1.9). It consists of a unilateral
palpebral oedema with conjunctivitis and swelling of the
regional lymph nodes. In'other cases, a skin nodule may
appear at the site of penetration by the parasite, appearing
1-2 weeks after the bite, and is called the 'chagoma of
inoculation', It must be emphasized, however, that. in
the majority of cases, the point of entrance cannot be
determined. We do not know of any reports of the
histological patterns of the portal of entry by biopsy.
Once in the vertebrate host. at the point of entrance, the
trypomastigotes enter tissue cells where they lose the
flagellum and replicate as rounded amastigotes. Later,
they reach the blood stream 'as trypomastigotes and
may thus reach other organs. Here, again, they become
amastigotes and produce a tissue reaction; in the heart
this takes the form of an acute diffuse myocarditis, The
amastigotes reproduce in the intracellular riests until they
rupture 2-4 weeks after formation (Fig. 1.10), and the
parasites 'disappear', In reality, they do not disappear;
they may return later to the blood stream in the flagellate
form (trypomastigotes) and so an endogenous re-infec-
tion may take place. In addition, they may be withdrawn
from the blood stream by another insect bite. Experimen-
tally, it has been shown recently that. in lower animals,
amastigotes are circulating in the blood stream and that
they are as infective as trypomastigotes 11 .
The pathogenesis of chronic Chagas myocarditis
remains unknown. This is, in part. due to the difficulty of
detecting parasites in the myocardium at this stage of the
disease and to the similarities between this and the tissue
reaction of so-called idiopathic myocarditis of Fiedler12.
Several theories of pathogenesis have been proposed 13-15.
The two most favoured hypotheses are the antiheart
immune or autoimmune reactions 16,17 and the neurogenic
theory of the influence of damage to the vegetative
nervous system 18.19 . There are several aspects of the
neurogenic theory which deserve comment: the morpho-
logical and functional bases of this theory were initially
obtained from study of Chagas disease patients at very
advanced stages of the disease 2o . More recent clinical 21 - 23
15
and experimental 24.25 studies indicate that myocardial
damage may precede the cardiac parasympathetic abnor-
malities. The reduction in the number of cardiac vagal
neurons 26 and the functional disorders of cardiac para-
sympathetic innervation 27 are also seen in patients with
ventricular dilatation who do not have Chagas disease. It
seems, then, that the cardiac parasympathetic abnorm-
alities are secondary to the progressive dilatation of the
cardiac chambers 28 .
We believe that chronic Chagas myocarditis may be due
to repeated exogenous and/or endogenous re-infections.
Pathology
The organs which may have intracellular amastigotes of
T. cruzi in man are those with various types of the
musculature cells: smooth muscle cells of the digestive
tract as well as skeletal muscle fibres and myocardial
muscle fibres. Damage of the latter is of most importance.
Furthermore, brain tissue may be affected with amastigote
nests in the glial cells; also, the placenta with subsequent
congenital trypanosomiasis and, rarely, the testicles. In
numerous autopsies performed by the authors, parasites
were looked for in the organs of the PMS (lymph nodes,
liver, spleen, bone marrow), in other parenchymal organs
and in the vegetative nervous system, but were not
found 29 . This is in contrast to the findings reported in
lower animals, amastigotes of T. cruzi may be located in
cells of numerous viscera.
Gross lesions in the acute form of Chagas disease are
observed in the heart (Figs. 1.11-1.13), brain and the
musculature of the digestive tract. including the tongue.
The heart shows hypertrophy and dilatation, the latter
developing in the final days with diminished consistency.
The myocardium may reveal a fish-flesh or cooked-meat-
like aspect or foci of various sizes of a yellowish-white
colour are found. In the brain, oedema and multiple
petechiae are observed.
In the chronic form, hypertrophy and dilatation,
mostly of the left ventricle are present. Coronary arteries,
even in older patients, are not usually affected. On the
surface of the heart. a subepicardial rosary, i.e. a chain of
small fibrotic nodules, is seen (Fig. 1.14). Quite often,
parietal aneurysms can be observed, in addition to various
numbers of whitish scars in the myocardium of variable
sizes and shapes. However, none of these lesions is
pathognomonic. This means that all these alterations may
also appear in cardiopathies with other aetiologies (Fig.
1.15), Aneurysms are mainly located at the apex of the
left ventricle; they are thin-walled showing fibrotic tissue
and contain thrombi (Fig. 1,16). From these thrombi,
arterial embolism often takes place with subsequent
infarction in numerous organs.
Regarding histology, the parasites appear in tissue
sections as amastigotes in intracellular nests, i.e. as
parasites without flagella. It must be emphasized that
characteristic kinetoplasts in the amastigotes are seen
mostly in preparations after recent penetration into tissue
cells and when the tissue is removed early and well
preserved. This means that these structures are not found
in each and every case, In tissue sections of routine
autopsies, we only rarely saw the kinetoplasts. We there-
fore stress that amastigotes are almost never recognized
as such, with all the structural details, in tissue sections.
They are mostly indistinguishable from other small micro-
organisms with the H&E stain.
Morphologically, amastigotes are also indistinguishable
from species of Leishmania. In order to differentiate
between these two, we must consider that each of these
parasites has particular and specific locations in tissues
and the corresponding organs. Small yeast cells are
16 PROTOZOAN DISEASES

Fig.1.8 Triatomines (Rhodnius prolixus) , vectors of

Chagas disease

Fig. 1.7 Nest of amastigotes of Trypanosoma cruzi in a g lial cell Fig.1.9 'Romaiia's sign ' in a Trypanosoma cruzi infected patient from
(pseudocyst). Rod-like kinetoplasts are visible. H&E Venezuela. This periorbital and unilateral oedema marks the site of entry
of the parasite

Fig. 1.11 Acute fatal form of Chagas disease with cardiomegaly

Fig.1.10 Ruptured nest of Trypanosoma cruzi in the acute myocarditis Fig. 1.12 Fish-flesh appearance of the myocardium in acute Chagas
of an infant. one month after becoming ill with fever. H&E myocarditis
PROTOZOAN DISEASES 17

Fig. 1.13 Whitish spots on the cut surface of myocardium in a case Fig.1.14 Subepicardial 'rosary' considered typical in cases of chronic
of acute Chagas myocarditis Chagas myocarditis

Fig.1.15 Acute myocarditis in an infant from Merida. Parasites could Fig.1.16 Apica l aneurysm of the left ventricle with thrombus in a case
not be found in tissues in this case of chronic myocarditis
18
Grocott-positive while small protozoan organisms gener-
ally are Grocott-negative. Outside muscle fibres and
glial cells, we have never seen parasites in other cells
(macrophages or endothelial cells).
The tissue reaction found at the level of myocardium
in the acute form is a marked cellular infiltration, more
or less diffuse (Figs. 1.17 and 1.18), where lymphocytes,
histiocytes and plasma cells can be seen while the number
of leukocytes is reduced. In wide areas, the muscle fibres
disappear because they have been totally replaced by the
infiltrates. This is a true myocarditis, apparently as a result
of the action of parasites present in variable numbers of
intracellular (myocardial fibres) nests. We are, therefore, at
a loss to understand why nowadays numerous researchers
call this typical inflammatory process of the disease
myocardiopathy, instead of myocarditis.
As far as the central nervous system is concerned, the
inflammatory process is disseminated and localized in the
white and grey matter. In the white matter, there is a
diffuse gliosis present. The reaction of the neurocytes is
mild and non-specific. The parasitic cells or nests of them
are hardly ever surrounded by cellular infiltrates. Notably,
the intracellular localizations of amastigotes are seldom
recognized as such with a light microscope. There are
three main types of lesions:
1. Small granuloma-like cell infiltrates (100-500 J.lm),
often situated near arterioles but also 'free' in the
parenchyma, composed of lymphocytes and histi-
ocytes as well as microglial rod-like cells.
2. Cuff-like cellular infiltrates in the perivascular Vir-
chow-Robins' spaces formed by lymphocytes, plasma
cells and monocytes.
3. Small glial nodules consisting of astrocytes with rod-
like microglial cells. A non-specific meningitis occurs
occasionally, in addition to acute Chagas encephalitis.
Primary Chagas meningitis has not. to our knowledge,
been reported (Figs. 1.19-1.23).
In other organs, the parasites cause a non-specific, often
scarce, inflammation, usually of the interstitial type (Figs
1.24-1 .28). In Chagas orchitis, parasites are located
inside seminiferous tubules, and cellular infiltrates are
present in the interstitium (Fig. 1.29).
In the chronic form, the heart is the main organ
involved. Lesions in the brain are not observed. The
chronic myocarditis shows areas of fibrosis of variable
size, with and without cellular infiltrates, either totally or
partially replacing the muscle tissue (Figs. 1.30-1.34). If
exclusive fibrosis is observed, without cellular infiltrates
or with only scarce ones, a diagnosis of myocarditis may
be questionable.
The cellular infiltrates are made up primarily of lympho-
cytes, histiocytes, plasma cells and, very rarely, neutro-
philic leukocytes. Sometimes, a variable number of eosi-
nophilic leukocytes is observed and, occasionally,
myogenous multinuclear giant cells are found. The origin
of the myogenous giant cells, i.e. that they grow from
muscle fibres, could be corroborated in one case, when
lipofuscin pigment was observed in a giant cell (Fig.
1.35). The presence of giant cells does not indicate a
granulomatous reaction because of the lack of epithelioid
cells. Micronecroses are found occasionally in cases of
chronic myocarditis as well as typical acute cardiac
infarcts.
I n the great majority of all these cases, parasites cannot
be found in the tissues in spite of intensive and prolonged
search. In practice, therefore the question arises of
whether one is faced with myocarditis due to infection
with trypanosomes or with the so-called 'chronic idi-
opathic myocarditis' which occurs allover the world and,
PROTOZOAN DISEASES
obviously, also in regions of endemic Chagas disease.
Regarding the so-called endomyocardial fibrosis, a
well-known entity in Africa and in some way related to
African trypanosomiasis, it cannot be ruled out that
this cardiopathy in South America has links with the
Trypanosoma cruzi infection. However, only few cases of
this sort have been observed in South America.
So-called mega-organs, mostly reported in Brazil,
Argentina and Chile, have not been found in Venezuela.
References
1. Schenone, H. and Rojas, A. (1989). Algunos datos y observaciones
pragmaticas en relaci6n a la epidemiolgia de la enfermedad de
Chagas. 801. Chil. Parasitol., 44, 66
2. Brass, K. (1955). Statistische Untersuchungen Ober die idiopathi-
sche Myokarditis im Raum Valencia, Venezuela. Frankf. Z. Path., 66.
77
3. Doehnert. H. R. and Motta. G. (1965). Enfermedad de Chagas y
miocarditis cr6nica. Arch. Venez. Med. Trop. Parasit. Med., 5, 124
4. Maeckelt. G. A. (1965). EI Diagn6stico Parasito-immunol6gico de
la Infecci6n Chagasica. Universidad Central de Venezuela, Caracas
5. Salfelder, K. (1971). Pathologisch-anatomische Probleme der
Chagas-myokarditis. Krongressber. II. Tag. Oester. Ges. Tropenmed ..
IV. Tag. Dtsch. Tropenmed. Ges. Verlags. Kont. H. Scheffler, Lue-
beck, p. 72
6. Sauerteig, E. (1978). Es todavia la enfermedad de Chagas un
problema de salud publica? Hospital "Dr. Luis Razetti", Barinas/-
Venezeula
7. Novoa Montero, D. A. (1983). Chagas' disease and chronic myo-
cardiopathy: An epidemiologic study of four Venezuelan rural
communities. Doctoral thesis. The Johns Hopkins School of Hygiene
and Public Health, Baltimore
8. Novoa Montero, D. A. (1990). Similar death rates among chagasic
and non-chagasic Venezuelan rural adults through a 12-yearfollow-
up study. XL Conven. An. ASOVAC. Cumana/Venezuela
9. Chandler. F. W. and Watts. J. C. (1988). Immunofluorescence as
an adjunct to the histopathologic diagnosis of Chagas' disease. J.
Clin. Microbiol.. 26. 567
10. Schottelius. J. (1984). Differentiation between Trypanosoma cruzi
and Trypanosoma rangeli on the basis of their sialic acid content.
Tropenmed. Parasit.. 35, 160
11. Ley. V .. Andrews, N. w., Robbins. E. S. and Nussenzweig, V.
(1988). Amastigotes of Trypanosoma cruzi sustain an infective
cycle in mammalian cells. J. Exp. Med.. 168. 649
12. Fiedler. F. (1899). Festschr. 4. Stadtkrankenhaus Dresden-
Friedrichstadt
13. Tanowitz. H. B. et a/. (1990). Enhanced platelet adherence and
aggregation in Chagas' disease: a potential pathogenic mechanism
for cardiomyopathy. Am. J. Trop. Med. Hyg.. 43. 274
14. Morris. S. A. et al. (1990). Pathophysiological insights into the
cardiomyopathy of Chagas' disease. Circulation. 82, 1900
15. Andrade. S. G. (1990). Influence of Trypanosoma cruzi strain on
the pathogenesis of chronic myocardiopathy in mice. Mem. Inst.
Oswaldo Cruz. 85, 17
16. Jaffe, R. Dominguez. A .. Kozma. C. and Gavaller. B. V. (1962).
Bemerkungen zur Pathogenese der Chagaskrankheit. Z. Tropenmed.
Parasit.. 12. 2
17. Cossio. P M. et a/. (1977). Chagasic cardiopathy. Immunopatho-
logic and morphologic studies in myocardial biopsies. Am. J.
Pathol.. 86, 533
18. Koeberle. F. (1959). Cardiopathia parasympathicopriva. Munch.
Med. Wschr.. 101. 1 308
19. Oliveira. J. S. M. (1985). A natural model of intrinsic heart nervous
system denervation: Chagas' cardiopathy. Am. Heart J.. 110, 1092
20. Amorim. D. S. et al. (1982). Chagas' disease as an experimental
model for studies of cardiac autonomic function in man. Mayo Clin.
Proc.. 57, 42
21.' Davila, D. F. (1988). Heart rate response to atropine and left
ventricular function in Chagas' heart disease. Int. J. Cardiol.. 21.
143
22. Fuenmayor, A. J. et al. (1988). The Valsalva maneuver. a test of
the functional status of cardiac innervation in chagasic myocarditis.
Int. J. Cardiol.. 18. 351
23. Casado. J .. Davila. D. F. et al. (1990). Electrocardiographic abnor-
malities and left ventricular systolic function in Chagas' heart
disease. Int. J. Cardiol.. 27. 55
24. Davila. D. F. (1988). Vagal stimulation and heart rate slowing in
PROTOZOAN DISEASES 19

Fig. 1.17 Acute diffuse chagasic myocarditis. Nests of parasites are Fig. 1.18 Acute chagasic myocarditis at higher power with muscle
difficult to discern at this magnification. H &E fibres replaced by cellular infiltrates and a nest of parasites faintly visible.
H&E

Fig.1.19 Acute chagasic encephalitis at low power. H&E Fig.1.20 Acute chagasic encephalitis with a marked perivascular cell
infiltrate. H&E

Fig.1.21 Nest of Trypanosoma cruzi amastigotes in the brain without Fig. 1.22 Parasitic nest in the cellular infiltrate of an acute chagasic
inflammatory reaction. Outlines of a glial cell not visible. H &E encephalitis. H&E
20 PROTOZOAN DISEASES

Fig.1.23 Necrobiotic cells in an acute chagasic encephalitis mimicking Fig.1.24 Marked inflammation in acute chagasic oesophagitis. H&E
parasitic structures. H &E

Fig.1.25 Acute chagasic enteritis. H&E Fig. 1.26 Acute chagasic colitis. Note parasites localized in the
digestive tract in muscle cells. H&E

Fig. 1.27 Nest of Trypanosoma cruzi amastigotes in placental villus. Fig.1.28 Same case as Fig. 1.27 at higher power. H&E
A case of congenital Chagas infection. H&E
 PROTOZOAN DISEASES 21

Fig. 1.29 Chagas orchitis with nests of parasites in a seminiferous Fig. 1.30 Chronic myocarditis with several myogenous giant cells.
tubule. Giemsa H&E

Fig.1.31 Chronic myocarditis with fibrosis and foca l cellular infiltrates. Fig.1.32 Chronic myocarditis with marked fibrosis and scarce cellular
H&E infiltrates. H&E
22 PROTOZOAN DISEASES

Fig. 1.33 Chronic granulomatous myocarditis of unknown aetiology. Fig. 1.34 Another case of chronic myocarditis with giant cells and
H&E undetermined aetiology. H&E

Fig. 1.35 Myogenous giant cell in a case of chronic myocarditis

showing granules of lipofuscin pigment. thus revealing the myogenous
origin of the giant cell. H &E
PROTOZOAN DISEASES
acute chagasic myocarditis. J Auton. Nerv. Syst., 25, 233
25. Gottberg, C. F. et at. (1988). Heart rate changes in acute chagasic
myocarditis Trans. R. Soc. Trap. Med Hyg., 82, 851
26. Amorim, D. S. and Olsen, E. G. J. (1982). Assessment of heart
neurons in dilated (congestive) cardiomyopathy. Sr. Heart J, 47,
11
2. AFRICAN TRYPANOSOMIASIS
Introduction
This infection is also known as sleeping sickness. Epi-
demics with high mortality rates had depopulated vast
regions of Africa, The preventive campaigns of the WHO
to control the vectors have had the result of limiting
considerably this disease. Also, it has been possible to
treat cases with effective drugs. However, eradication of
vectors has not been total; still more or less important
epidemics occur, WHO experts believe that, in spite of all
efforts, complete extermination of this disease will not
take place in the near future,
Natural infections occur in domestic and wild animals 1 .
The disease may be produced by inoculation into labora-
tory animals 2- 5 (Fig. 2.1).
In African trypanosomiasis, histological preparations
do not show the parasites as amastigotes, in contrast to
American trypanosomiasis. This must be emphasized as
the most important morphological difference between
these two parasitoses.
The infection is limited to equatorial Africa. Two forms
of the disease may be distinguished: in the western and
central parts of this continent, a chronic and relatively
benign disease is observed 6 In the later stages, symptoms
of the CNS appear and the outcome may be fatal In the
eastern parts of the continent, on the other hand, the
disease takes a more severe course. In untreated patients,
death occurs, frequently 1-3 months after infection 7
Clinical diagnosis in early stages of the disease may be
made by observing trypomastigotes in blood smears and
smears of puncture fluids taken from the chancre, lymph
nodes, body cavities and also of the spinal fluid, Cultures
can be made on artificial medias or by inoculation of
rodents and monkeys,
The parasite
The three species of African trypanosomes belong, like
Trypanosoma cruzi. to the genus Trypanosoma and the
family Trypanosomatidae. Trypanosoma brucei gambi-
ense is responsible for human infection in the western
and central parts of the continent, Trypanosoma brucei
rhodesiense in eastern parts and Trypanosoma brucei
brucei is only a pathogen in domestic animals. All three
are structurally identical. They differ in their pathogenicity
in man and lower animals
Both T. gambiense and T. rhodesiense each have a
specific group of vectors, live in different geographical
regions and have different reservoir hosts, They do infect
superior vertebrates, but, in general, do not cause disease;
that is, these animals are reservoir hosts and a source of
infection for man but do not become ill. On the other
hand, domestic animals, such as horses, donkeys, camels,
dogs and cats, fall ill when infected by trypanosomes
belonging to the species T. brucei brucei. The disease is
called 'Ngana', which means 'useless' or 'weak' and has
a fairly high mortality rate. Some wild animal species,
certain domestic animals and man, on the other hand, do
not become ill when infected by T. brucei brucei.
The three species appear only in the flagellate form
(trypomastigotes) and have variable sizes (Fig 22).
Trypomastigotes succumb fast: a good fixation is required
23
27. Amorim, D. S. (1981). Is there autonomic impairment in (conges-
tive) dilated cardiomyopathy. Lancet, 1, 525
28. Davila, D. F. (1989). Cardiac parasympathetic abnormalities. Cause
or consequence of Chagas' heart disease? Parasitol. Today, 5, 327
29. Sauerteig, E. (1991). Chagaskrankheit. In Trapenmedizin in Klinik
und Praxis. Thieme Verlag, Germany (in press)
to preserve them, In stai ned smears, the trypomastigotes
measure 1.5-3.5,um in width and 15-30,um in length,
including the flagellum. The nucleus stains dark with the
Giemsa, Wright and other similar stains and is situated
towards the centre,
The trypomastigotes are difficult to recognize in
unstained smears because they are colourless, thin and
transparent. However, it is possible to detect them when
they are alive because of their motility. This type of
trypanosome has a small kinetoplast situated near the rear
end. The flagellum originates in the blepharoplast near
the kinetoplast, which, however, is not identifiable with
a light microscope. Trypanosomes of this type may multi-
ply by longitudinal division of the trypomastigote. This is
in contrast to Trypanosoma cruzi which reproduces only
in the amastigote form.
Man is the principal reservoir host for T brucei gambi-
ense, but wild and domestic animals (pigs for example)
may act as reservoir hosts. However, wild animals (above
all anti lopes) and also domestic animals are the principal
hosts for T. rhodesiense, infection from man to man being
less frequent.
The vector for T. brucei gambiense and T. brucei
rhodesiense is the tsetse fly (Fig. 2.3), Glossina palpalis
and Glossina morsitans, respectively, These species do
not have important structural differences, Either male or
female fly may act as vector.
Pathogenesis
When the non-infected tsetse fly (Glossina spp.) bites an
infected man or lower animal, it sucks blood and, with it,
the trypanosomes, which then reach the intestinal tract
of the vector. The parasites multiply in the gut of the fly
and three weeks later they reach the salivary glands, in
the meantime having become metacyclic and infectious.
Therefore, when an infected fly bites a healthy man, it
transmits the trypanosomes. This bite, by the way, is
painful. At the site of the bite, which is almost always the
cervical region, a skin nodule is produced and inflam-
mation of the regional lymph nodes develops. Both
lesions constitute the 'inoculation chancre' of the African
trypanosomiasis, also named Winterbottom's symptom
(Fig. 2.4). From this focal cutaneous lesion, haematogen-
ous dissemination results, with clinical manifestations of
fever, general malaise and splenomegaly. In experiments
recently carried out on lower animals, it has been found
that the parasites first reach the meninges; encephalitis
develops later in addition to the meningitis 2
Pathology
Both the gross and the microscopic lesions are similar in
the two forms of African trypanosomiasis 9 . The CNS,
lymph nodes, spleen and heart are all involved and
sometimes there are effusions in all corporal cavities. In
the central nervous system oedema and petechiae are
found as gross lesions. The lymph nodes and the spleen
may be enlarged. Apparently, no other gross manifes-
tations have been observed and no specific gross features
characteristic for this infection are known.
24 PROTOZOAN DISEASES

Fig. 2.1 Numerous amastigotes of Trypanosoma rhodesiense in a Fig. 2.2 Numerous trypanosomes of Trypanosoma gambiense in a
villus of the choroid plexus. Experimental infection of a mouse (H. blood smear. Giemsa
Schmidt. 1983) Giemsa

Fig.2.3 Tsetse fly (Glossina), vector of African trypanosomiasis Fig.2.4 Skin chancre. Residual scar of an infection in African trypano-
somiasis
PROTOZOAN DISEASES 25

Fig.2.5 Typical perivascular infiltrates in the encephalitis of sleeping Fig.2.6 Perivascular infiltrate with a 'morula cell", H&E
sickness, H &E

Fig. 2.7 Higher magnification of a perivascular infiltrate in African Fig. 2.8 Numerous 'morula cells' in a case of cryptococcosis with
trypanosomiasis encephalitis, H &E brain lesions, H&E

Fig.2.9 Higher magnification of a 'morula cell' in African trypanosomi- Fig.2.10 Leptomeningitis in a case of African trypanosomiasis ence-
asis encephalitis. Note the confluence of the intraplasmatic corpuscles, phalitis
H&E
26
Under the microscope, the causative agent cannot be
found in tissue sections as is the case in the acute form
of Chagas disease. Only in experimental animals are
parasitic elements seen in the tissues, and amastigotes
and trypomastigote-like forms have been reported 2 .
Regarding tissue reaction, the inflammation is present
in the white and grey matter and there are regions
with oedema. Here, also, progressive forms of astroglial
elements are seen with an homogeneous eosinophilic
cytoplasma which is irregularly shaped (gemistocytic
transformation). Neurocytes do not show any specific
lesions.
In the often-dilated perivascular spaces. cellular infil-
trates, consisting of lymphocytes, plasma cells and mono-
cytes are found. In addition, there are many 'corpuscular
structures', measuring from 20-30 Jlm in diameter, which
are strongly eosinophilic, spherical or ovoid in shape, and
situated in the cellular infiltrates or in the oedematous
areas. They consist of small eosinophilic bodies measuring
2-3 Jlm in diameter. either showing a morula aspect or
appearing homogeneous. The latter is due to confluence
of the small bodies. These structures represent Russell or
Mott bodies and are characteristic of this disease but are
also observed in cases of encephalitis due to other
aetiologies. We have seen them in encephalitis due to
Cryptococcus neoformans or Histoplasma capsula tum
var. capsula tum. Mononuclear inflammation is seen also
in the pia mater spreading along blood vessels into the
cerebral cortex (Figs. 2.5-2.9).
In enlarged lymph nodes and the spleen, a reactive
hyperplasia and infiltrates of histiocytes and plasma cells
are seen histologically. In the infrequently encountered
pancarditis, Iymphohistiocytes and plasma cells are
observed in infiltrates of the endocardium, myocardium 1o
and the pericardium. Occasionally, fibrosis of variable
degree is also present at these sites.
Endomyocardial fibrosis, frequently seen in Africa, is
usually of undetermined aetiology. Nevertheless, it has
been interpreted as a possible residual lesion of pancarditis
caused by trypanosomes 11 .12 .
The authors of this atlas were able to review personally
LEISHMANIASES
Traditionally, three types of disease are produced by
species of the genus Leishmania:
1. The cutaneous leishmaniasis or oriental sore, seen in
the Old World and caused by Leishmania tropica
(Wright) .
2. The mucocutaneous leishmaniasis, seen in the New
World and due to Leishmania braziliensis (Vianna).
3. The visceral leishmaniasis or Kala-azar, seen in both
the Old and New World, and produced by Leishmania
donovani (Laveran, Mesnil).
There are arguments against this classification; mainly that
skin lesions may be seen in all three types. Nevertheless, it
is useful from the geographical point of view and for
other practical reasons.
Some features common to the three species of leish-
manias must be emphasized:
1. The amastigotes of the three species of Leishmania
(and of Trypanosoma cruzi) are structurally identical
PROTOZOAN DISEASES
only a limited number of histological preparations of a
few cases of sleeping sickness provided by friends.
Together with other colleagues, we believe that the
absence of causative agents in tissues, as reported in the
literature, may be because histology has not been carried
out systematically and thoroughly after postmortem exam-
inations.
References
1. Schoening, B. (1989) The dog as reservoir host of Trypanosoma
brucei gambiense. Trop. Med Parasit.. 40, 500
2. Schmidt. H. (1983). The pathogenesis of trypanosomiasis of the
CNS. Virchows Arch. (pathol. Anat.). 399, 333
3. Sudarto, M. W (1990). Immunohistochemical demonstration of
Trypanosoma evansi in tissues of experimentally infected rats and a
naturally infected water buffalo (Bubalus bubalis). J Parasitol.. 76,
162
4. Emeribe, A O. et a/. (1990). Platelet aggregation inhibition in
Trypanosoma vivax infection of sheep Cent. Afr. J Med, 36, 1
5. Grootenhuis, J. G. (1990). Susceptibility of African buffalo and
Boran cattle to Trypanosoma congolense transmitted by Glossina
morsitans central is. Vet. Parasitol., 35, 219
6. Sachs, R.. Mehlltz, D. and Zillmann, U. (1984). Sleeping sickness in
West-Africa: parasitological-epidemiological field studies in Liberia.
Zbl. Bakt. HVg. A. 258, 384
7. East African Trypanosomiasis Research Organization Report. (1965).
Authorities of the East African Common Services Organization
8. Brun, R.. Jenni, L., Schoenenberger, M. and Schell. K. F. (1981).
In vitro cultivation of bloodstream forms of Trypanosoma brucei, T.
rhodesiense, and T. gambiense. J Protozool.. 28, 470
9. Poltera, A A, Ows, R. and Cox, J. N. (1977). Pathological aspects
of human African trypanosomiasis (HAT) in Uganda. Virchows
Arch. Abt. Path. Anat., 373, 249
10. de Raadt. P. and Koten. J. W. (1968). Myocarditis in Rhodesian
trypanosomiasis. E. Afr. Med J, 45, 128
11. Brink, A J. and Weber, H. W. (1966). Endomyocardial fibrosis
(EMF) of East. Central and West Africa compared with South
African endomyocardiopathies. S. A Med J, 40, 455
12. Poltera, A A and Cox, J. N. (1977). Pancarditis with valvulitis in
endomyocardial fibrosis (EMF) and in human African trypanoso-
miasis (HAT). A comparative histological study of four Uganda
cases. Virchows Arch. Abt. A Path. Anat.. 275, 53
and therefore these species cannot be distinguished
in tissues.
2. The leishmanias do not show flagellate forms (trypo-
mastigoes) in mammalian blood.
3. The leishmanias (and trypanosomes) may be cultured
in the artificial NNN medium. This medium (Nory,
McNeal, Nicolle) contains bactoagar, sodium chloride,
distilled water and. in addition, defibrinated blood,
from diverse animal species, and penicillin.
Many details of the pathogenesis of the different types
of leishmaniasis and of the virulence of their causative
agents still need to be investigated. The gross and micro-
scopic features of cutaneous and mucocutaneous leish-
maniasis are similar. The only difference is that the
mucosae may be involved in the latter.
We describe the mucocutaneous leishmaniasis in most
detail; our personal experience has been ggined studying
leishmaniasis in the New World.
PROTOZOAN DISEASES
3. CUTANEOUS LEISHMANIASIS
Introduction
This infection is called also oriental sore or boil, tropical
ulcer, sore of Jericho, Ale~~o, Delhi or Biskra, or leish-
maniasIs of the Old World - .
The disease occurs in the Mediterranean region, Asia
Minor, India, China and Africa stretching from east to
west between the 10° and 13° of latitude. Natural infec-
tions exist in several lower animal species 4 Rodents may
be used for experimental purposes 56 .
Three types of the disease are considered the urban
type (L. tropica minor) which is mostly anthropozoonotic;
the rural type (L. tropica major) which is zoonotic; and
the diffuse cutaneous leishmanias (L. tropica aethiopica).
The two types first mentioned usually show solitary
lesions. The last is characterized by multiple lesions. This
is apparently due to an anergic disposition of unknown
origin; the Montenegro skin test in this type is negative.
The cutaneous leishmaniasis may heal spontaneously.
Clinical diagnosis is made by confirmation of the causing
agents in smears or biopsies; also, fine needle aspiration
biopsy may be performed 7
The parasite
Leishmania tropica is encountered in tissues in the amasti-
gote form. The amastigotes are spherical. measure 2-4 11m
in diameter and show a kinetoplast. Structurally, the
amastigotes of all the Leishmania species are identical,
not only the species causing the cutaneous, mucocu-
taneous and visceral leishmaniasis (L. tropica, L. brazili-
ensis and L. donovam"). but also L. tropica minor, L.
tropica major and L. tropica aethiopica. It is therefore
difficult to understand why different names were given
to the leishmanias producing the different clinical forms
of the disease.
The reservoir host for the urban form of L. tropica is
predominantly man; for the rural form of cutaneous
leishmaniasis, however, dogs, cats, rodents and monkeys
Vectors of the disease are female sand flies of the genus
Phlebotomus.
Pathogenesis
Infection takes place through the bite of a sand fly
(Fig. 3.1), mostly on uncovered parts of the skin. The
incubation period varies from 2-8 months. Usually, a
solitary skin nodule develops which grows slowly and
may later ulcerate and become a scar.
Multiple skin lesions appear to be due to an anergy of
unknown origin. There is no satisfactory explanation at
present for the differences in localization of the lesions
in the two forms of leishmaniasis found in different
geographical regions, i.e. why, in case of the cutaneous
leishmaniasis, neither mucosae nor internal organs are
affected.
Pathology
In the great majority of cases, a single skin lesion is found
The urban type of cutaneous leishmaniasis is characterized
4. MUCOCUTANEOUS LEISHMANIASIS
Introduction
This disease is also named American tegumentary leish-
maniasis or leishmaniasis of the New World and has been
confirmed as an autochthonous infection from Northern
Argentina to Southern Mexico 1 • The name depends on
27
by the so-called 'dry' form of the disease, i.e. the skin
nodules do not have a tendency to ulcerate. When it
relapses, it is called 'lupoid leishmaniasis'. In the rural
type, on the other hand, there is a tendency to ulcerate
and then it is called the 'humid' form.
While only solitary skin lesions used to be seen in the
L. tropica infection, recently multiple lesions, mainly in
the face, have been described, mostly in certain regions
of Africa. This form of the disease which was unknown
in the Old World previously, is called diffuse tegumentary,
lepromatoid, keloid or tuberculoid leishmaniasis. These
cases of leishmaniasis with single or multiple lesions in
the skin are practically identical to the leishmaniasis
lesions in the New World; lesions are limited to the skin
without involvement of the mucosae (Figs. 3.2 and 3.3).
In some reports recently, it was stated that. histolog-
ically, the tissue reaction in the American form of leish-
maniasis shows special patterns which allow differen-
tiation from the disease in the Old World. However, as
yet. these data have not been confirmed.
As we do not have much personal experience of
leishmaniasis of the Old World, we shall refrain from
giving detailed descriptions of this infection. The few
cases we could examine showed infiltrates of numerous
plasma cells, a pattern not. perhaps, so pronounced in
the mucocutaneous leishmaniasis. In a case of cutaneous
leishmaniasis of the Old World, numerous parasites were
seen (Fig. 3.4) All the following details of mucocutane-
ous leishmaniasis also apply to the cutaneous form. Only
the data about epidemiology and, of course, all details
about the involvement of the mucosae relate solely to the
American leishmaniasis.
References
1. Price, E. W. and Fitzherbert. M. (1965) Cutaneous leishmaniasis in
Ethiopia Med. J, 3, 57
2. Bryceson, A. D. (1969). Diffuse cutaneous leishmaniasis in Ethiopia,
I. The clinical and histological features of the disease. Trans. R. Soc.
Trop Med. HVg, 63, 708
3. Pringle, G. (1957). Oriental sore in Iraq. Historial and epidemiologic
problems. Bull. Endem. Dis. (Baghdad). 2,41
4. Mutinga, M. J., Kihara, S. M .. Lohding, A., Mutero, C. M., Ngatia,
T. A. and Karanu, F. (1989). Leishmaniasis in Kenya description of
leishmaniasis of a domestic goat from Transmara, Narok District.
Kenya. Trap. Med. Parasitol, 40, 91
5. Krampitz, H. E. (1981). Primary and secondary skin leishmaniasis in
experimental rodent hosts. Zbl Bakt. HVg. I Abt. Orig. A., 250, 191
6. Cillari, E. et al. (1990). Rapid quantitative method for measuring
phagocytosis of Leishmania promastigotes using a double radiolabel-
ling method. J Immunol. Meth., 130, 57
7. Akhtar, M. et al. (1991). Diagnosis of cutaneous leishmaniasis by
fine needle aspiration biopsy; report of a case. Diagn. Cvtopathol..
7,172
the particular anatomical locations and the country or
region (Mexico, Panama, Peru, the Guianas, Amazonas
or Brazil) Some other local names are 'chicleros' ulcers',
espundia, buba, uta and pianbois (forest yaws). The
disease is well known in Venezuela 2- 5 . It is usual to
28 PROTOZOAN DISEASES

Fig. 3.1 Phlebotomus, male. This genus of sand-flies is the vector for Fig. 3.2 Early stage of leishmanial infection in the Old World
all the species of leishmanias. Only the females are vectors

Fig. 3.3 Advanced or chronic stage of oriental sore with a single skin Fig. 3.4 Oriental boil. Case from Afghanistan with numerous parasites
ulcer in this field. H &E
PROTOZOAN DISEASES
observe groups of patients with this infection, not single
cases, in rural areas with abundant woods and vegetation.
Natural infections occur in dogs and certain wild lower
animal species. Experimentally, visceral lesions may be
produced in hamsters by inoculation with L. braziliensis6 .
Cutaneous lesions are similar to those of the Old World,
but usually more extensive and not as easily cured as the
latter. The mucosal lesions are located in the oral or nasal
cavity and may lead to perforation of the nasal septum or
the pharyngeal wall. Prognosis is less favourable than in
the cutaneous leishmaniasis of the Old World.
Clinical diagnosis is made by confirmation of the
causative agent in biopsies or smears from the surface of
ulcerations. The cutaneous test of Montenegr0 7 is positive
in more than 75%. The immunoperoxide method facilitates
diagnosis 8 .
The parasite
Leishmania braziliensis is the causative agent of muco-
cutaneous leishmaniasis. Other species described as
causative agents are apparently only subspecies or vari-
ants of L. braziliensis. This may be the case, for instance,
in the 'new species' isolated in the Venezuelan Andes by
Scorza et a/. in 1978 9 . Also Leishmania mexicana'o will
not be considered here since it is of no importance in
this context. This species may be differentiated from L.
braziliensis by using DNA probes".
L. braziliensis has one form with (in the vector and in
cultures) and one without flagella. The aflagellate forms,
leishmanias or amastigotes, measuring 2-3 J-lm in diam-
eter, are found in mammalian tissues (Fig. 4.1). They are
slightly smaller than the amastigotes of Trypanosoma
cruzi and the nucleus is situated on the edge attached to
the cellular membrane, which is thin and often not
discernible. The rod-like kinetoplast of the amastigotes
may be easily seen in well-preserved recently infected
tissue, which has been fixed immediately after being
removed from the patient. I n tissues of routine biopsy
material, we have not seen kinetoplasts. but have seen
them convincingly in selected cases only.
It must again be emphasized that Leishmania brazili-
ensis is structurally identical to Leishmania tropica and
Leishmania donovani. as well as to the amastigotes of
Trypanosoma cruzi.
Reservoir hosts for L. braziliensis are rodents. certain
wild animal species and, more rarely, dogs which show
cutaneous lesions produced by L. braziliensis.
Vectors are females of sand fly species belonging to
the genus Phebotomus or Lutzomyia. for instance L.
longipalpis. In Venezuela. the most important vector is
Phlebotomus panamensis.
Pathogenesis
When the females of infected phlebotomes (sand flies)
bite healthy men or lower animals. they inject promasti-
gotes into the superficial layers of the dermis. Here, they
lose their flagella and penetrate into histiocytes. or are
phagocytosed by macrophages. The inflammatory reac-
tion leads to a nodular skin lesion which becomes visible
between 2 weeks and 4 months after the bite of the
insect.
If a patient has several leishmania lesions, three patho-
genic possibilities exist:
1. They are the result of multiple bites.
2. They originated through autoinoculation from a single
primary lesion as a result of a single bite. or
3. There was a haematogenous dissemination with the
consecutive appearance of multiple skin nodules.
29
The diffuse tegumentary leishmaniasis starts. apparently,
with a single nodule which probably spreads haemato-
genously. producing multiple skin lesions. This process
may take years.
Why and how involvement of the facial mucosae occurs
mostly is not clear. Probably. it is due to haematogenous
dissemination. However. in the course of parasitaemia,
involvement of the internal organs never takes place.
Pathology
Mostly. lesions are found in areas of the skin usually not
covered by clothing. Weeks or months after the bite. one
or several papules develops or skin nodules appear.
reaching variable dimensions. Later. they ulcerate and
become chronic lesions; when untreated. there is no
tendency to spontaneous healing. On the whole they are
difficult to differentiate from skin afflictions due to other
causes. especially as they have a chronic evolution (Figs.
4.2-4.9).
The clinical form known as 'diffuse tegumentary leish-
maniasis' with multiple skin lesions shows characteristic
papulomatous nodules in contrast to the solitary or
isolated lesions of the common leishmaniasis (Fig. 4.10).
The nodules become confluent and are transformed into
cauliflower-fike lesions which present a papillomatous
appearance with an irregular surface. Characteristically.
epidermal ulceration does not occur regularly12.
The lesions in the mucosae are localized in the nose,
oral cavity (Fig. 4.11). pharynx. larynx and trachea. and
mayor may not be accompanied by cutaneous lesions.
In cases without active cutaneous lesions. a scar in the
skin may indicate a former primary cutaneous infection
by leishmanias. The alterations of the mucosae vary
considerably in shape and size and are often tumour-like
with ulcerations. Sometimes, they produce stenosis and
occlusions in the upper parts of the respiratory and
digestive tract which occasionally require surgery.
Exceptionally. the amastigotes are observed histolog-
ically in epithelial cells of the epidermis or the mucosae;
predominantly they are encountered inside the histiocytes
where they reproduce by division and lead to clusters of
parasites inside individual tissue cells. The cytoplasm of
these tissue cells often shows a clear or vacuolized aspect
and. consequently. these cells seem to be 'small cysts'.
Numerous histiocytes with clear cytoplasm and many
parasites are seen. mainly in acute infections and in
diffuse tegumentary leishmaniasis. When the parasitized
histiocytes rupture. the liberated amastigotes invade other
cells or are phagocytosed by other macrophages. It must
be emphasized that the liberated and single amastigotes
outside tissue cells are difficult to recognize as such and.
therefore. diagnosis cannot be made. The number of
leishmanias in each inflammatory focus is very variable.
If they are present in great numbers. the intracellular
leishmanias are easily recognizable in the 'vacuoles' of
histiocytes which. however. are frequently empty due to
the loss of parasites during the cutting procedures. On
the other hand. if they are scarce or situated extracellularly.
or in smears. their visualization may be difficult and often
it is impossible to see them I n addition to their intracellular
localization in histiocytes with a clear cytoplasm. the
borders of necrotic areas should be reviewed in order
to detect leishmanias. When the parasites are clearly
recognizable. the kinetoplast is not usually well preserved
(Fig. 4.12). Some parasitologists insist upon making a
diagnosis of leishmanias only when kinetoplasts are
visible. We have not often seen kinetoplasts in our material
and would like to stress that our experience leads us to
make a diagnosis of leishmanias only when organisms
are Grocott-negative.
30 PROTOZOAN DISEASES

Fig. 4.1 Numerous amastigotes of Leishmania braziliensis arranged in Fig. 4.2 Muco~cutaneous leishmaniasis. Large ulcerative lesion of the
clusters. Thick section. Giemsa nose

Fig. 4.3 Muco~cutaneous leishmaniasis. Profound ulcer with perfor~ Fig. 4.4 Muco~cutaneous leishmaniasis. Deep skin lesion with defect
ation of the ala nasi of the ear lobe

Fig. 4.5 Muco~cutaneous leishmaniasis. Papulomatous lesions with Fig. 4.6 Muco~cutaneous leishmaniasis. Large skin ulcer with a
haemorrhages granular ground on an arm
PROTOZOAN DISEASES 31

Fig. 4.7 Muco-cutaneous leishmaniasis. Deep skin ulcer with sharp

borders on a thigh

Fig. 4.10 Multiple nodular foci in the face, typical of 'diffuse tegu-
mentary leishmaniasis', also called 'leproid'

Fig. 4.8 Muco-cutaneous leishmaniasis. Large skin ulcer with thick

borders on a finger

Fig. 4.9 Typical leishmaniatic skin scar Fig. 4.11 Muco-cutaneous leishmaniasis. Extensive lesions in the
mucosa of mouth, pharynx and nose
32
I n our material. parasites have been confirmed in tissue
sections in only 50% of all cases of mucocutaneous
leishmaniasis 13 ,14, Even scarcer were the parasites in other
series of routine biopsies 15 ,
When making a differential diagnosis, histiocytes with
clear or vacuolated cytoplasm are commonly observed in
skin and mucosa in lesions of leprosy, rhinoscleroma and
histoplasmosis capsulati,
I n addition, amastigotes of L braziliensis in tissues
must be differentiated from amastigotes of leishman ias of
other species and Trypanosoma cruzi, Furthermore,
Toxoplasma gondii and small yeast cells, e,g, Histoplasma
capsula tum var, vapsulatum, species of Candida, Toru-
lopsis glabrata and Penicillium marneffei must be dis-
tinguished, as well as other small forms of yeast cells in
mycoses which normally show large yeast cells in tissues,
such as Coccidioides immitis, Blastomyces dermatitidis
and Paracoccidioides brasiliensis, Fungus cells may be
ruled out when the elements under discussion are Gram-,
PAS- and Grocott-negative, Before making a histological
diagnosis of leishmaniasis, we always perform the Grocott
test 16 Haematoxylin-positive chromatin particles may also
look like leishmanias in tissues (see reference 17, Chapter
23).
Tissue reaction in skin and mucosa lesions is identical
The factors which determine the type of tissue reaction
are:
1. The stage of evolution and the duration of the disease,
2. The virulence of the species or strain of the infectious
leishmanias,
3, The human organism's immunological status,
4, The presence or lack of a secondary infection, and
5, The action of drugs in cases where the patient receives
treatment.
What is usually seen is a diffuse tissue reaction with
dense cellular infiltrates composed of a variable number
of Iympho- or histiocytes, plasma cells and, occasionally,
mast cells and/or eosinophilic granulocytes. If there are
numerous histiocytes with clear cytoplasm and intracellu-
lar parasites, some scientists call the tissue reaction
'histiocytoma' In a recently observed case with marked
infiltrates of histiocytes showing a clear cytoplasm con-
taining numerous amastigotes (Figs. 4.13 and 4.14), a
unique (for us) feature was detected: a single multinuclear
giant cell contained several tissue cells which harboured
amastigotes This means that there was a double phago-
cytosis: first amastigotes were engulfed by histiocytes
and later the histiocytes were engulfed by a giant cell
(Fig. 4.15).
In addition to diffuse cellular infiltrates, one can also
observe granulomatous reactions with epithelioid and
giant cells, Epithelioid granulomas sometimes show cen-
tral necroses, features which are indistinguishable from
granulomas caused by Mycobacterium tuberculosis, We
have not seen as many cases with typical granulomas,
Instead, there have been quite numerous instances when
the exclusive presence of epithelioid cells leads to the
diagnosis of leishmaniasis (Figs, 4,16-4.19),
Pseudoepitheliomatous hyperplasia of the epidermis is
typical of chronically ulcerated leishmanial lesions, but
this feature is also found in chronic cutaneous lesions of
deep mycoses and in other chronic dermatopathies,
Exudation of granulocytes and microabscesses are not
common in mucocutaneous leishmaniasis. When granulo-
cytes are found, they are mostly located near the surface
of a tissue defect at the base of an ulceration, M icro-
abscesses are the typical lesions in infection due to
Sporothrix schenckii,
PROTOZOAN DISEASES
We were never able to confirm the presence of parasites
in lymphangitis or regional lymphadenitis which are
common in patients with leishmania lesions, This is
probably because the patients were not examined at the
right time or because these lesions in the lymph nodes
were due to secondary bacterial infections, However,
experimentally, parasites have been confirmed in regional
lymph nodes of lower animals 1B The differences that exist
between the leishmaniases of the Old and New World
have not been elucidated. Further studies are needed on
this subject.
In the rather rare 'diffuse tegumentary leishmaniasis',
tissue reaction shows numerous histiocytes with clear
cytoplasm containing many parasites in the inflammatory
foci; a granulomatous reaction is never observed,
The lack of parasites in tissues in numerous apparently
chronic cases makes it imperative, in practice, to give at
least a presumptive histological diagnosis based only on
a more or less characteristic tissue reaction,
References
1, Pessoa, S, B, and Barreto, M, p, (1948), Leishmaniose Tegumentar
Americana, Min, de Educacao e Saude, Rio de janeiro
2, Pifano, F, and Scorza, j, v, (1960), Aspectos immunol6gicos de
las leishmanias que parasitan al hombre, con especial referencia a
la Leishmania brasiliensis Pifano, Medina y Romero, 1957, Arch.
Venez. Med Trap, Parasit, Med, 111, 16
3, Kerdel-Vegas, F, (1966), Histopatologia de la Leishmaniasis amer-
icana, Med Cutanea, 3, 267
4, Convil. j" Rodriguez, G" Henriquez, A j, and Medina, R, (1968),
H istopatologia de la Leishmaniasis Tegumentaria Americana, Derm
Venez., XI, 475
5, Pons, R" Serano, H, and Marmol Leon, p, (1974), Incidencias de la
Leishmaniasis tegumentaria americana en poblaciones del Dtt Mir-
anda del Edo, Zulia (Venezuela), Kasmera (Univ, del Zulia), 5, 31
6, Kahl, L p, eta!. (1991), Leishmania (Viannia) braziliensis: compara-
tive pathology of golden hamsters infected with isolates from
cutaneous and mucosal lesions of patients residing in Tres Bracos,
Bahia, Brazil, Am J Trap, Med Hyg" 44, 218
7, Montenegro, j, (1926), A cutis-reaccao na leishmaniose, Ann. Fac,
Med Sao Paulo, 1, 323
8, Salinas, G, et a!. (1990), Detecci6n de amastigotes en leishmaniasis
CU1<lnea y mucocutanea por el metodo de immunoperoxidasa,
usando anticuerpo pol iclonal: sensibilidad y especifidad comparadas
con metod os convencionales de diagnostico, Mem Ins!. Oswaldo
Cruz, 84, 53
9, Scorza, j, V, Valera, M" Scorza, C. de, Carnevali, M" Moreno, E,
and Lugo-Hernandez, A (1979) A new species of Leishmania
parasite from the Venezuelan Andes region, Trans. R. Soc Trap,
Med Hyg, 73, 293
10, Piekarski, G, (1987), Medical Parasitology, Springer-Verlag
11, Barker, D, C. and Butcher, j, (1983), The use of DNA probes in
the identification of leishmanias: discrimination between isolates of
the Leishmania mexicana and L braziliensis complexes, Trans, R.
Soc, Trap, Med Hyg" 77, 285
12, Goto, H, et a!. (1990), A case of multiple lesion mucocutaneous
leishmaniasis caused by Leishmania (Vianna) braziliensis infection,
J Trap, Med Hyg,. 93. 48
13, Salfelder, K, (1971), Erfahrungen bei der pathologisch-anato-
mischen Diagnose von tiefen Mykosen und Parasitosen, Beitr Path.,
143, 197
14, Arriaga, A D, de (1977), Leishmaniasis Muco-cutanea en los
Hospitales de Merida y Barinas, Trabajo de Ascenso, Fac, de Med,
ULA Merida
15, Sotto, M, N" Yamashiro Kanashiro, E, H" da Mata, V L, and de
Brito, T, (1989), Cutaneous leishmaniasis of the New World
diagnostic immunopathology and antigen pathways in skin and
mucosa, Acta Trap, Basel.. 46, 121
16, Grocott, R, G, (1955), A stain for fungi in tissue sections and
smears, using Gomori's methenamine silver nitrate technique, Am
J Clin. Path" 25, 975
17, Salfelder, K. Liscano, T, R, de and Sauerteig, E, (1990) Atlas of
Fungal Pathology Kluwer Academic Publishers
18, Travi, B" Rey-Ladino, j, and Saravia, N, G, (1988), Behavior of
Leishmanias braziliensis s, 1, in golden hamsters: evolution of the
infection under different experimental conditions, J Parasitol, 74.
1059
PROTOZOAN DISEASES 33

Fig.4.12 Numerous amastigotes of Leishmania braziliensis arranged Fig.4.13 Muco-cutaneous leishmaniasis. Numerous histiocytes with
diffusely and in clusters. Giemsa and Wright clear or vac uolic cytoplasm . The parasites have fallen out during the
process of cutting and staining. H&E

Fig.4.14 Higher magnification of lesions in Fig. 4.13 with preserved Fig.4.15 Same case as Figs. 4.13 and 4.14. Giant cell with a 'double
leishmanias in a histiocyte. H&E phagocytosis'. First. macrophages engulf leishmanias and then the giant
cell phagocytoses the leishmania-containing macrophages. H&E
34 PROTOZOAN DISEASES

Fig.4.16 Muco-cutaneous leishmaniasis. Typical epithelioid cell reac- Fig. 4.17 Muco-cutaneous leishmaniasis. Dense cell infiltrates and
tion. Furthermore, small nests of parasites (intracellularly located) are granulomatous reaction with giant cells. H &E
seen. H&E

Fig. 4.18 Muco-cutaneous leishmaniasis. Granulomatous reaction Fig. 4.19 Muco-cutaneous leishmaniasis. Dense cellular infiltrate and
with giant cell and necrosis, H&E numerous 'clear' epithelioid cells. This is a characteristic histological
feature of chronic leishmaniasis. Parasites are mostly not visible. H&E
PROTOZOAN DISEASES
5. VISCERAL LEISHMANIASIS
Introduction
This disease is called also kala-azar, which means black
fever, or tropical splenomegaly, as well as 'infantile
anaemia with tumour of the spleen'. The prevalence of
this infection is low. The vector has been controlled
by anti-anopheles campaigns, but has not been totally
eradicated.
The infection is endemic in the countries surrounding
the Mediterranean Sea, the Middle East. Asia, Africa and
South America; only a few cases are reported in Central
America and Mexico and human cases of Kala-azar are
known in Venezuela 56 .Mostly, children are affected l - 4
Dogs, canine species and wild animals (foxes and
several rodent species) can be naturally infected? Experi-
mentally, mice, dogs, monkeys, cats, hamsters and other
animals may be inoculated 8- 10
Anaemia, increased IgG and marked splenomegaly are
the clinical signs. Almost 90% of untreated patients die
1-2 years after the beginning of the disease. With current
therapy, almost 90% can be cured. Visceral leishmaniasis
has also been fou nd in AIDS patients n
Clinical diagnosis is made by confirmation of the
causative agent. for instance, in biopsies of the bone
marrow, culture and inoculation into laboratory animals.
The parasite
Leishmania donovani is the causal agent of the disease
in man and lower animals. The amastigotes of L. donovani
have the same structu re as L. tropica and L. braziliensis
and are called Leishman and Donovan (L-D) bodies*. L.
donovani chagasi is a new clinical variant of cutaneous
leishmaniasis in Honduras 12
Amastigotes of L. don 0 vani, as well as the other species
of Leishmania stain well in mammalian tissues with H&E
and Giemsa and are negative when the methods of
Gram, PAS and Grocott are used. They are situated in
intracellular clusters inside the histiocytes and phagocytes
of the PMSt. They have either a spherical or an oval
shape, and measure 1.5-3,um in diameter (Fig. 5.1). They
are s.llghtly smaller than the amastigotes of Trypanosoma
cruZ!, but otherwise cannot be distinguished from the
latter. I n smears, they appear to be larger than in tissue
sections. The nucleus and kinetoplast may be seen in well-
preserved material. When kinetoplasts are not detected in
the tissue sections, it is due to the age, degeneration or
necrobiosis of the amastigotes, or it may be that the tissue
was not preserved in time or in the correct man nero
The flagellate forms of L. donovani, the promastigotes,
are found in cultures at temperatures of 20-30°C. Charac-
teristically, as in other species of leishmanias, flagella are
not encountered in the blood of mammals.
Reservoir hosts of L. donovani vary according to geo-
graphiC region: man almost exclusively in India; dogs and
other canine species in Mediterranean countries; man and
certain wild animals, but not dogs, in Africa. Wild and
domestic animals are reservoir hosts in South America.
For information about asymptomatic carriers of the dis-
ease, see under Pathogenesis below.
Vectors are species of the genus Phlebotomus (sand
"The so-called Donovani bodies, however, are causal agents of inguinal
granuloma. a quite different nosologic entity.
tpMS = phagocytic-mononuclear (cell) system and has replaced RES
(reticulo-endothelial system from Aschoff) and RHS (reticu lo-histiocytic
system).
35
flies) and, in the New World, mosquitos of the genus
Lutzomyia.
Pathogenesis
The bite of an infected female sand fly almost always
produces the so-called 'Ieishmanioma', a circumscribed
skin nodule which soon disappears. In some cases, this
nodule does not appear or is not noted by the patient.
General malaise, fever and weakness, signs of generalized
disease, appear 2-6 months later.
In man, as well as in lower animals, asymptomatic
carriers of kala-azar are known to have parasites in the
dermis without visible alterations of the skin. These
asymptomatic carriers play an important role in the trans-
mission of the infection.
Pathology
The main organs involved are the spleen, the liver (Fig.
5.2), bone marrow, lymph nodes (Figs. 5.3-5.6) and the
lymphatiC tissue of the digestive tract (Figs. 5.7 and 5.8).
In addition to spleno- and hepatomegaly (the latter less
pronounced), there are no characteristic gross features of
this infection.
Cutaneous lesions, as manifestations of a late form of
kala-azar, have been described in India. This so-called
'cutaneous leishmaniasis post-kala-azar' is sometimes
observed 1-2 years after a patient was thought to have
been cured The clinical late form shows spots which
slowly enlarge and form nodules of a lepromatous aspect;
usually, they do not ulcerate. The 'Ieishmaniomas' of the
skin in the primary infection soon disappear, as noted
above.
Clinically a differential diagnosis must be made,
especially in infants, with generalized histoplasmosis
capsulatl. However, the latter is fatal in a very short time,
whereas the progression of kala-azar is slower. In any
splenomegaly occurring in endemic areas, kala-azar must
be considered.
Histologically, parasites (amastigotes of L. donovant')
are plentiful in the organs of the PMS. They are located
In clusters inside histiocytes. Occasionally, they are also
located in liver cells; here, they must be looked for with
an electron microscope 13 In the other organs, they are
less numerous. It is a 'must' to rule out small yeast cells
by application of special fungus stains. With HE, the
parasites stain well. With the indirect immunoperoxidase
method, they may be marked specifically14
Amastigotes of L. donovani are scarce in histiocytes in
cases of chronic kala-azar (Figs. 5.9-5.11) and in the
cutaneous nodules of the late form of the disease. It is
most important to make a differential diagnosis with
histoplasmosis capsulati in view of the characteristic
location of the small yeast cells and the amastigotes inside
histiocytes
Tissue reaction in the visceral leishmaniasis is not
characteristic. When numerous parasites are present in
tissues, there is practically no tissue response. When
parasites are scarce, marked infiltrates of lymphocytes
and, above all. plasma cells, are seen with numerous
typical Russell bodies (Figs. 5.12 and 5.13).
36 PROTOZOAN DISEASES

Fig. 5.1 Kala-azar. Numerous leishmanias (Leishmania donovam) are

seen near a large cell nucleus in the smear of a human bone marrow.
Kinetoplasts cannot be recognized. H&E

Fig.5.4 Same case as Fig. 5.3 at higher magnification. H&E

Fig. 5.2 Kala-azar. Nests of leishmanias (Leishmania donovani) are

seen clearly in macrophages of a portal field in the liver in a case of an
acute infection. H&E

Fig. 5.3 Numerous intracellular nests of leishmanias (Leishmania

donovani) in mesenteric lymph node of a human case at low power.
H&E
Fig.5.5 Same case as Figs 5.3 and 5.4 at higher magnification. H&E
PROTOZOAN DISEASES 37

t,

Fig. 5.6 Same case as Figs. 5.3-5.5 at a still higher magnification. Fig. 5.7 Kala-azar. Human small intestine with thickened villi of the
Kinetoplasts, however. cannot be detected. H&E mucosa due to numerous leishmania-containing macro phages. H&E

Fig.5.8 Villus of the mucosa from Fig. 5.7 at higher power. Numerous Fig.5.9 Liver tissue in case of chronic kala-azar at low power. H&E
intracellular organisms of Leishmania donovani may be seen. H &E
38 PROTOZOAN DISEASES

Fig. 5.10 Same case as Fig. 5.9 at higher magnification. Nests of Fig.5.11 Same case as Figs. 5.10 and 5.11 at a still higher mag-
leishmanias (Leishmania donovani) may be seen in Kupffer cells. H&E nification. Parasites and cell infiltrate may be recognized. H&E

Fig. 5.12 Kala-azar. Human lymph node with numerous Russell Fig.5.13 Kala-azar. Human spleen with two large cells (plasma cells)
bodies. H&E containing Russell bodies. Parasites may not be discerned. Fibrine.
PROTOZOAN DISEASES
References
1. Heilmann. A. Doehnert. G. and Wohlenberg. A (1971). T6dlich
verlaufende Leishmaniasis visceral bei Mittelmeerurlaubern. Dtsch.
Med Wschr.. 96. 31
2. Loehr. H. and Wolf, H. (1978). Viszerale Kala-azar-Erkrankung beim
Kind. Dtsch. Med Wschr.. 103. 424
3. Alencar. J. E. (1978). Leishmaniose visceral no Brazil. Rev. Med
Univ. Fed Ceara. 17. 129
4. Gottstein. U .. Steiner. K.. Hank. H .. Klimaschewski. G. and
Sedlmeyer. I. (1975). Kala-azar eine wichtige Krankheit nicht nur
der Tropen. Dtsch. Med Wschr.. 100. 2022
5. Martinez. N. A and Pons. A R. (1941). Primer caso de Kala-azar
en Venezuela. Gac. Med Caracas. 48. 329
6. Pifano. F. (1954). Estado actual del Kala-azar en Venezuela. Arch.
Venez Pat. Trap .. 2. 213
7. Swenson. C. L.. Silverman. J .. Stromberg. P. c.. Johnson. S. E..
Wilkie. D. A. Eaton. K. A and Kociba. G. J. (1988). Visceral
leishmaniasIs in an English foxhound from an Ohio research colony.
J Am. Vet. Med Assoc .. 193. 1089
8. White. M. R. Chapman. W L. Jr. and Hanson. W L (1989). A
6. GIARDIASIS
Introduction
A synonym for this parasitosis is lambliasis. The infection
occurs worldwide; 2-10% of the population. mostly
children. are infected in countries with a cold or temperate
climate. In countries with a warm climate. the percentage
goes up to 20-50%1. The prevalence among subjects at
risk in certain countries is not negligible 2 In Venezuela
this intestinal infection is well known.
Dogs. cats and rodents are carriers of the parasite and
may be used for experimental pu rposes 3,4
Clinically. diarrhoea with yellowish fetid faeces are
observed. occasionally accompanied by abdominal pain
and cramps; also steatorrhoea 5 and malabsorption syn-
drome have been found. Prognosis is always favourable;
there are no reports of a fatal outcome. Infection is
symptomatic in children but usually asymptomatic in
adults 6
Clinical diagnosis is made by confirmation of mobile
trophozoites in the duodenal contents 7 . Cystic forms of
giardias are found in faeces. Giardiasis often occurs in
combination with another bacterial or viral enteritis.
The parasite
Giardia lamblia or Lamblia intestinalis is a flagellated
protozoan with vegetative (trophozoites) and cystic
forms. The trophozoites are pear-shaped. measure 10-
12 f1m in length. 5-10 f1m in width and are 3-5 f1m thick.
They possess 2 nuclei and 4 basal corpuscles near the
round anterior pole. These 4 corpuscles. found between
the two nuclei. are the origin of the 8 filaments which
appear as 4 pairs of flagella outside the parasite. On the
ventral surface. there is a so-called 'suction disc'. visible
only with an electron microscope. which corresponds to
a circumscribed shallow part used by the parasite to
attach itself to the intestinal mucosa.
The cysts of Giardia lamblia are oval and have 4 nuclei.
situated at one pole. They measure 8-14 f1m in length
and 6-10 f1m in width. In the interior of the cyst. one
can see longitudinal filaments which reach beyond the
membrane as short flagella. There are between two and
four basal corpuscles shaped like a sickle or a banana.
The cysts survive in a humid environment for weeks or
months 8
The giardias stain well with the Giemsa. H&E. and iron
haematoxylin. They are Grocott-positive (Figs. 6.1-6.5).
To see the structural details. fresh live giardias must be
used with special methods of fixation and phase contrast.
39
comparison of experimental visceral leishmaniasis in the opossum.
armadillo and ferret Lab. Anim. Sci.. 39. 47
9. Laurenti. M. D. et aJ. (1990). Experimental visceral leishmaniasis:
sequential events of granuloma formation at subcutaneous inocu-
lation site. In!. J Exp. Pathol.. 71. 791
10. Lujan. R. et a/. (1990). Leishmania braziliensis in the squirrel
monkey development of primary and satellite lesions and lack of
cross-immunity with Leishmania donovani. J Parasitol.. 76. 594
11. Falk. S.. Helm. E. B.. Hubner. K. and Stutte. H. J. (1988). Dissemi-
nated visceral leishmaniasis (kala-azar) in acquired immunodefici-
ency syndrome (AIDS). Pathol. Res. Prac!.. 183. 253
12. Ponce. C. et a/. (1991). L donovani chagasi: new clinical variant
of cutaneous leishmaniasis in Honduras. Lancet. 337. 67
13. Duarte. M. I.. Mariano. O. N. and Corbett. C. E. (1989). Liver
parenchymal cell parasitism in human visceral leishmaniasis. Vir-
chows Arch. A.. 415. 1
14. Ferrer. L. Rabanal. R. M. Domingo. M .. Ramos. J. A and Fondevila.
D. (1988). Identification of Leishmania donovani amastigotes in
canine tissues by immunoperoxidase staining. Res. Vet. Sci.. 44.
194
Pathogenesis
The cystic forms of G. lamblia in the faeces of man
or animal carriers contaminate water and foods. i.e.
transmission occurs from man to man or animal to man
directly and orally Some insects and other small animals
may also act as vehicles (seldom).
In the small bowel. cysts become trophozoites which
attach themselves by means of the rims of the 'suction
discs' to the superficial cells of the microvilli of the
mucosa. Here they multiply copiously by fission but do
not penetrate into the tissues.
It seems that it is the massive reproduction of giardias.
with the resulting microlesions and the production of
large amounts of mucoid substances. that leads to the
enteritis. Other theories have also been put forward as
pathogenic factors 9 • e.g. the mechanical prevention of
interchange of alimentary substances.
Pathology
The trophozoites of Giardia lamblia are found in the
duodenum. sometimes in the jejunum and. occasionally.
in the upper parts of the ileum. Location at other sites
has not been confirmed. The cysts are located in the
lower parts of the small intestine. in the large bowel and
in formed faeces. Gross intestinal lesions have not been
reported.
Histologically. the material obtained routinely in
autopsies cannot be used for studying giardias or the
lesions caused by these parasites. Biopsies must be
performed and the material then examined under an
electron microscope 10- 12
The attachment of the giardias to the surface of the
mucosa apparently acts as an irritant with the subsequent
inflammation. In acute cases. infiltrates of neutrophilic
and eosinophilic granulocytes are found in the stroma of
the upper parts of the mucosa and. in chronic cases.
Iymphohistiocytic ones are seen 13.
Ulceration of the mucosa. which is occasionally
observed. is not thought to be due to giardias but to other
infectious agents. such as bacteria or viruses.
References
1. Faust. E. C. and Gonzalez-Mugaburu. L. (1965) Parasitological
surveys in Cali. Departamento del Valle. Colombia. Xl. Intestinal
parasites in ward Silva. Cali during four years period. 1956-1960.
Am. J Trap. Med Hyg.. 14. 276
40 PROTOZOAN DISEASES

a b

c d

Fig. 6.1 Giardias in faecal smear of an autopsy. H&E Fig.6.2 Trophozoites (a and b) and cysts (c and d) of Giardia /amb/ia.
Giemsa

Fig. 6.4 Giardias in a smear of intestinal content. Autopsy material.

Grocott

"

Fig. 6.3 Cluster of Giardia /amb/ia trophozoites in faeces. Trichrom Fig. 6.5 Giardias and yeast cells (of Candida sp. 7) in smear of
intestinal content. Autopsy material. Grocott
PROTOZOAN DISEASES
2. Cotte-Roche. C. etal. (1991). Role de la giardiase dans la dyspepsie
non ulcereuse. Presse Med.. 20. 936
3. Arashima. Y. et al. (1990). Studies on the giardiasis as the zoonosis.
Kansenshogaku-Zasshi. 64. 295
4. Romia. S. A. et al. (1990). Virulence of Giardia lamblia isolates to
laboratory mice. J. Egypt Soc. Parasitol.. 20. 633
5. Amini. F. (1963). Giardiasis and steatorrhea. J. Trop Med. Hyg..
66.190
6. Peterson. H. (1973). Clinical significance of G. lamblia (Lamblia
intestinalis). Acta Hepatogastroenterol. (Stuttg.). 20.449
7. Gonzalez Carbajal Pascual. M .. Cayon. R.. Perez. A. and Sotto. A.
(1988). Value of endoscopic smears of the duodenal mucosa in the
diagnosis of giardiasis in adults. Rev. Gastroenterro!' Mex. 53. 37
8. de Regnier. D. P. Cole. L .. Schupp. D. G. and Erlandsen. S. L
(1989). Viability of Giardia cysts suspended in lake. river. and tap
water. App/ Environ. Microbiol.. 55. 1223
7. TRICHOMONIASIS
Introduction
This disease (for which there is no synonym) is endemic
allover the world. The infection is observed predom inantly
in promiscuous females but males may be infected 1 .
Trichomoniasis is common in Venezuela.
Trichomonas vagina/is is not found in lower animals.
although other species of this genus have been detected
in squirrel monkeys2. and systemic trichomoniasis has
been found recently in squabs (young pigeons).
The infection is almost always asymptomatic or latent.
Once symptoms appear, the infection remains active for
a long time. causing complaints like vaginal flux and
marked prurigo. Even with efficient therapy, patients are
not always cured by a single treatment as relapses and
reinfection are frequent. Clinical exacerbation, common
during menstruation and pregnancy. has been ascribed
to changes in pH of the vaginal milieu.
Clinical diagnosis may be confirmed by examination of
vaginal. cervical or prostate secretions and/or urine; the
typical mobile flagellates can be found in fresh specimens.
In asymptomatic females, trichomoniasis is often found
when cytological examinations (Papanicolaou) are made
in order to rule out a carcinoma.
Trichomoniasis is quite often associated with previous
bacterial. viral or mycotic infections of the urogenital tract
and with carcinoma of cervix. It has been confirmed.
however, that this parasitosis is not a carcinogenic risk.
The parasite
Trichomonas vagina/is is the only pathogenic species in
this genus. Other flagellates found in the digestive tract
and in the oral cavity of man are almost always apatho-
genic 3 .
The parasite is almost always pear-shaped and meas-
ured 7-30/lm in length (on average 13/lm). The size
varies with the type and strain, and the pH of the medium.
At the anterior end, a blepharoplast is seen, and from this,
originate 4 anterior flagella and one posterior flagellum
with an undulating membrane. The nucleus is situated
towards the rear end. In fresh preparations, the parasites
can be seen moving with the aid of their flagella and the
undulating membrane. They stain well with H&E, iron
haematoxylin, Giemsa or the Papanicolaou method (Figs.
7.1 and 7.2) In cultures (Fig. 7.3), the parasites may
phagocytose leukocytes, bacteria and red blood cells.
Leukocytes and epithelial cells are able to phagocytose
parasites 4 .
Pathogenesis
An infected male transmits the infection from one female
to another through sexual relations. The reservoir host of
41
9. Ament. M. E. and Rubin. C. E. (1972). Relation of giardiasis
to abnormal intestinal structure and function in gastrointestinal
immunodeficiency. Gastroenterology, 62. 216
10. Takano. J. and Yardley. J. M. (1965). Jejunal lesions in patients
with giardiasIs and malabsorption. An electron microscopic study.
Bu/!. Johns Hopkins Hosp .. 116. 413
11. Rosekrans. P eM. Lindeman. J. and Meijer. C J. L M. (1981).
Quantitative histological and immunohistochemical findings in
jejunal biopsy specimens in giardiasis. Virchows Archiv. A. (Patho!.
Anat), 393. 145
12. Khanna. R. et al. (1990). An ultrastructural analysis of changes in
surface architecture of intestinal mucosa following Giardia lamblia
infection in mice. Gastroentero!. Jpn .. 25. 649
13. Oberhuber. G. and Stolte. M. (1990). Giardiasis analysis of
histological changes in biopsy specimens of 80 patients. J. Clin.
Patho!.. 43. 641
Trichomonas vagina/is is the infected female.
There may also be indirecttransmission through sanitary
installations or infected underwear. I nfection of new-
born babies is due to contamination during parturition.
Pathology
In the female. the parasite lives in the vagina. in the
cervical channel, in the urethra and. occasionally. in the
lower part of the bladder 5 In males, they have been found
in the urethra and the prostate; some observers have also
noted them in the seminal vesicles 6 . Invasion of human
tissues by Trichomonas vagina/is has not been reported.
Gross lesions are not known.
The histological alterations which may be produced by
these parasites can be summarized in the following
manner:
1. The epithelial cells may degenerate and show cytoplas-
mic vacuolization (Fig. 7.4),
2. Regeneration and endocervical metaplasia of the epi-
thelial cells may occur (Fig. 7.6),
3. Inflammation with Iympholeukocytic and plasma cell
infiltrates may be seen in the epithelium and in the
stroma,
4 Erosions of the surface and mucopurulent exudation
may occur (Fig. 7.5).
It is not entirely clear whether these alterations are due
to the irritation produced by these parasites or due to a
secondary bacterial infection. It has been established,
however, that the parasites do not cause endometritis.
puerperal infections, sterility, miscarriages or carcinoma.
The parasites may produce some alterations in tissue
cells which could be confused with those seen in neoplas-
tic processes Therefore. if there is infection with this
parasite, it must be taken into consideration when cytol-
ogy and b.iopsy specimens are examined in order to avoid
a false positive diagnosis of malignancy.
Cytologic differential diagnosis of the parasite must
consider: artificial particles, as a result of contaminated
slides, epithelial cells or their nuclei. and deformed gran-
ulocytes, histiocytes or degenerated parabasal cells.
References
1. Feo. L G. (1944). The incidence and significance of Trichomonas
vaginalis infestation in the male. Am. J. Trop. Med.. 24. 195
2. Scimeca. J. M. Culberson. D. E.. Abee. C R. and Gardner. W. A. Jr.
(1989). Intestinal trichomonads (Trichomonas mobilensis) in the
natural host Saimiri sciureus and Saimiri boliviensis. Vet. Patho!.. 26.
144
42 PROTOZOAN DISEASES

Fig. 7.1 Smear from the uterine cervix. Organisms of Trichomonas Fig. 7.2 Higher magnification of a smear from uterine cervix. Papa-
vaginali~and leukocytes. Papanicolaou nicolaou

,. I • •

Fig.7.3 Smear of cultured parasites with visible flagella. Giemsa Fig.7.4 Trichomoniasis. Vacuolic degeneration of epithelial cells and
inflammation at epithelium and stroma. H&E

Fig. 7.5 Trichomoniasis. Islet of epithelial metaplasia (detached) at Fig. 7.6 Trichomoniasis. Erosion and marked inflammation at the
the endocervix. H&E endocervix. H&E
PROTOZOAN DISEASES
3. Honigberg. B. M. (1978). Trichomonads of importance in human
medicine. In Kreier. J. P. (Hrsg) Parasitic Protozoan II. Academic
Press: New York London San Francisco
4. Asami, K. (1952). Bacteria-free cultivation of Trichomonas vaginal is.
Kitasato Arch. Exp. Med., 25, 149
5. Heckel. N. J. (1936). A study of the pathologic alterations in the
8. AMOEBIASIS
Introduction
This disease is also called amoebic dysentery. It is still
an important infection, with involvement mainly of the
digestive tract. However, it may be treated successfully
with modern drugs when an early diagnosis is made.
When extraintestinal organs are involved, aetiological
diagnosis is not easily made.
The prevalence of amoebiasis is approximately 10% of
the world population and it occurs in practically all
countries and all social groups1. The disease is frequently
more severe in tropical and subtropical regions. Amoebi-
asis is endemic in Venezuela; in the fifties and sixties
numerous fatal cases were still observed in Merida/Vene-
zuela2.3. Epidemic outbreaks may occur simultaneously
with bacterial dysentery.
Natural Entamoeba histolytica infections are found in
dogs, rats, pigs and monkeys but they are of no relevance
to the human infection. Rats and other laboratory animals
may be used as experimental models4-7.
The dysenteric syndrome is characterized by blood and
mucoid substances in the diarrhoeal stools. Relapses,
after variable periods of apparent cure, are more frequent
than definitive cures of an acute stage.
Clinical diagnosis is made by confirmation of the
causative agent. This requires well-trained laboratory
personnel since other species of amoebae must be ruled
out and not all elements which are mobile in fresh
preparations represent amoebae. Also, in biopsies and
sections of cell blocks of a semiliquid material. amoebae
are sometimes difficult to distinguish from tissue cells
and other elements 8.9 . Serological diagnosis is indicated,
above all. in patients with liver abscesses 1o .
The parasite
Entamoeba histolytica is the only pathogenic species of
the intestinal amoebae, i.e. this species may invade tissues.
The other four species of intestinal amoebae (Entamoeba
coli, Endolimax nana, Iodamoeba buetschli/~ Dientamoeba
fragilis) are non-invasive. Soil amoebae are mentioned in
the next section, Acanthamoebiasis.
Two forms of Entamoeba histolytica exist the trophozo-
ites and the cysts. The former can be seen in diarrhoeal
stools and in tissues; the latter are found in formed faeces
and are able to survive outside the human organism
representing an 'enduring form'.
The trophozoite measures 7-35 jl.m, is irregularly
shaped and moves by typical amoeboid pseudopodia in
fresh preparations. The nucleus is vesiculous or annular.
In the cytoplasm, erythrocytes, fragments of tissue cells
or engulfed leukocytes are often present (Fig. 8.1). After
the division of trophozoites, cysts develop. These are
amoebae with thicker membranes. The cysts are spherical
and measure on average 11 jl.m. A young cyst has one
nucleus; a mature one up to four nuclei.
We are more inclined to examine permanent and stained
preparations than to look at unstained smears. For smears
and tissue sections, the classical stain is iron haematoxylin
(Heidenhain) which is somewhat better than haematoxy-
lin-eosin. We prefer a modification of the PAS method 11
43
female bladder and urethra resulting from infection with Trichomonas
vaginal is. J. Urol.. 35, 520
6. Crowley, E. (1964). Trichomonas prostatis and trichomenorrhea. A
new link in the diagnosis and treatment of trichomoniasis. J. Urol"
91, 302
(Fig. 8.2). Amoebae also stain partially with the Grocott
method.
Amoebae may be cultured in diverse artificial media.
They may harbour H IV -1 but there is no transmission to
human cells 12 .
Pathogenesis
The amoebic cysts are the infectious elements of Enta-
moeba histolytica. They reach the human digestive
tract through water, food or by other means, such as
dirty hands or indirect vectors such as flies. The most
important source of infection is man; a carrier of cysts
is generally asymptomatic and apparently completely
healthy. Patients with signs of amoebic dysentery are not
the source of infection; they eliminate only trophozoites
which die quickly.
When the cysts of E. histolytica reach the digestive
tract they transform into trophozoites which are able to
penetrate the wall of the large bowel. They migrate
through the mucosa and may reach the serosa through
all the layers of the intestinal wall. The classical concept
is that the vegetative forms (trophozoites) themselves
produce proteolytic (cyto- and histolytic) enzymes (as
indicated by the name Entamoeba histolytica) in order to
facilitate the penetration of tissues but this has not been
convincingly demonstrated. Be that as it may, the parasitic
invasion leads to tissue necrosis. The action or co-action
of bacteria, before and after formation of necroses, is also
not clear. There is always an associated bacterial infection.
Lately, both in amoebiasis and in other pathological
intestinal conditions, the necroses have been interpreted
as being lesions similar to infarcts. This means that the
necroses can be explained as the result of the formation
of thrombi or microthrombi which produce ischaemic
processes and consecutive infarcts. However, true thrombi
have not been found in our series of cases of amoebic
colitis.
The amoebae spread by contiguity, by lymphogenous
and haematogenous dissemination from primary intestinal
lesions (and from other sites). Haematogenous spread is
the most frequent and important while dissemination by
contiguity or contact is less common, and lymphogenous
spread is an exception. The large bowel and the liver are
the preferential organs for amoebic infections. From the
liver, they can also reach other viscera. Frequently, these
amoebae are encountered in an organ or organ system
distinct from the intestine, appearing to be an 'isolated
disease' because the intestinal lesions have recovered
and the patients may not even remember the diarrhoeal
episodes which possibly occurred only once years ago.
Pathology
Intestinal amoebiasis. The incubation period has not
been precisely defined. The superficial necrotic lesions in
the mucosa soon detach and multiple large ulcerative
areas remain in the mucosa, involving deeper layers of
the intestinal wall (Figs. 8.3-8.6). These ulcers in the large
intestine are deep crater-like defects with undermined rims
and are called 'button-hole' ulcers (Figs. 8.7 and 8.8).
44 PROTOZOAN DISEASES

8 b

c d
Fig.8.2 Tropholoites of Entamoeba histolytica in tissues
Fig. 8.1 Tropholoites of Entamoeba histolytica in tissues. H&E
a. Erythrophagia. H&E
b. Special stain for amoebae. PAS
c. Marked amoebae at intestinal mucosa. Grocott
d. Amoebae . Grocott

Fig.8.3 Amoebiasis. Large intestine with deep mucosal ulcer showing Fig.8.4 Amoebiasis. Numerous necrotic foci and ulcers in the mucosa
thick borders of the large intestine
PROTOZOAN DISEASES 45

Fig. 8.5 Amoebiasis. Small and large necrotic focI In the mucosa of Fig. 8.6 Amoebic colitis with carcinoma of the colon transversum.
the large intestine Under the microscope in this lesion adenocarcinoma in addition to
amoebae was found It was not possible to determine which of these
two processes was the in itial one

;,

Fig. 8.7 Amoebiasis. A complete. characteristic 'buttonhole ulcer' of Fig. 8.8 AmoebiasIs. A recently formed ulcer involving mucosa and
the large intestine comprising mucosa and submucosa with the borders submucosa of the large intestine in the form of a 'buttonhole'. H&E
of the entire circumference undermined. H&E

Fig. 8.9 'Amoeboma' of the mesocolon. The opened large Intestine Fig,8,10 Solitary amoebic liver abscess
presents an enlarged (cut) fistula connecting intestinal lumen with a
large 'tumour' which shows a cavity (necrosis) on the central part. The
'tumour' is formed by chronic granulation tissue with numerous amoebae
in the mesocolon
46
However, it must be noted that ulcers with these charac-
teristics are also found in bacterial dysentery and that
they do not appear exclusively in amoebiasis. In our
material, the ulcers of the amoebic colitis do not occur
more frequently at any particular site in the large bowel:
they occur in the caecum, both flexurae or in the rectosig-
moidal region. Relatively frequently, the appendix showed
amoebic lesions, although large grossly detectable lesions
were not seen at this site. More frequently, the appendix
and part of the ileum were involved, showing, microscop-
ically, more or less extensive necrotic lesions in the
intestinal wall, but almost never grossly visible ulcers.
Isolated amoebic appendicitis is not common 13. The
amoebic ulcers in the large intestine, which are often deep,
may reach the serosa where circumscribed peritonitis is
provoked. Perforation of these ulcers with consequent
diffuse peritonitis, which used to be a serious compli-
cation, is no longer seen, apparently because diagnosis
is made earlier and/or therapy is more efficient.
Other important complications are peri-appendicular
abscesses and colo-abdominal, colo-gastric or colo-hep-
atic fistulae. Fistulae between the colon and renal pelvis,
rectum or bladder are rarer. Amoebic lesions of the spleen,
pancreas and kidneys are formed rarely by contiguity.
In chronic intestinal amoebiasis, with or without
mucosal ulcers, the mucosa becomes thicker and polypoid
tumoral lesions form. These are the basis of the extensive
chronic inflammation of the intestinal wall. Many authors
believe that strictures, stenosis, scars of the intestinal wall
and peritoneal adhesions are the result of chronic lesions
caused by amoebae. However, we have looked for this
type of sequel for many years in our autopsy and biopsy
material and have never been able to attribute them to
amoebic infections.
The lesions named 'amoebomas' and 'amoebic granu-
lomas' need a brief discussion: Many cases described as
'amoebomas', 'amoebic granulomas', lesions of an 'X-ray
aspect of a large tumour' or an 'inflammatory parasitic
pseudotumour' do not merit this denomination They
correspond solely to a circumscribed thickness and/or
dilatation of an intestinal segment in an amoebic infection,
with the exception of a few cases, e.g. a reported amoe-
boma really similar to a carcinoma 14
One of our cases showed amoebic alterations of a
tumourous appearance and probably merits a denomin-
ation of resemblance to a tumour (see Fig. 8.9). An
intestinal segment of the large intestine had been resected
with the' presurgical clinical diagnosis of carcinoma of
the colon. In the surgical specimen, a large chronic para-
intestinal abscess in the mesocolon was found which was
in contact with the intestinal lumen through a 'not open
perforation', i.e. a fistula. The central necrotic masses of
this abscess, where numerous amoebae were found, were
surrounded by a broad fibrotic shell. The 'large nodule'
observed in this case w.as, in truth, very similar to a tumour
or neoplasm and should be called a peri- or para-intestinal
amoeboa.
In more than 30 years, only one case of amoebic colitis
and an apparently coincident carcinoma of the colon has
been seen in our material. However, primary carcinomas
at this site are rare in our autopsy and biopsy material in
comparison with other countries.
Hepatic amoebiasis. The amoebae reach the liver,
usually by means of the portal vein, and there they
produce either single (Fig. 8.10) or multiple (Figs. 8.11
and 812) pylephlebitic abscesses. The solitary amoebic
abscesses previously described as being typical are the
exception rather than the rule 15 . The amoebae first cause
necrotic foci which may be confused with tumours or
tumour metastases. Later, the foci become soft in the
central parts and, on the whole, look like abscesses with
a semiliquid necrotic content. often similar to chocolate
PROTOZOAN DISEASES
because of massive old haemorrhages. The formation of
a liver abscess by contiguity due to amoebiasis of the
colon transversum is exceptional. Diagnosis of amoebic
liver abscesses may be difficult 15 .
Hepatomegaly (Fig. 8.13) in cases of amoebic colitis
may occur without amoebic abscesses in the liver. In this
case, the enlargement of the liver is due to an infectious-
toxic reaction of this organ or a secondary infection, but
not necessarily to the parasites. The hepatomegaly has
been called 'amoebic hepatitis', but this name does not
seem appropriate since, in these cases, amoebae are not
present in the liver. The name 'reactive hepatitis' may be
more suitable. When amoebae invade hepatic tissue, they
produce abscesses but not amoebic hepatitis. Complica-
tions which may occur in this type of cases are:
1. Peripherical abscesses may perforate Glisson's capsule
and drain towards the abdominal cavity, the stomach,
pancreas, spleen or through the abdominal wall (Fig.
8.14) .
2. Skin fistulae may originate in the right upper abdominal
region.
3. Subdiaphragmatic or subphrenic abscesses may result
which may perforate the diaphragm and cause pleural
and pulmonary lesions with formation of abscesses or
hepato-bronchial fistulae, mostly in the lower lobule
of the right lung (Figs. 8.15 and 8.16). Amoebic
abscesses in the lower lobule of the left lung are less
frequent and are the result of amoebic lesions in the
left lobe of the liver.
4. Rarely, amoebic lesions have been found in the pericar-
dium and in the oesophagus.
5. Sometimes, metastatic abscesses resulting from hae-
matogenous dissemination are formed in the lung.
6. Rarely, E. histo/ytica produces brain abscesses (Fig.
8.17). I n the two latter instances, the poi nt of departure
may have been an amoebic lesion in the large intestine
or an amoebic liver abscess.
Rare extraintestinal amoebic lesions. In addition to
the relatively frequent extraintestinal lesions mentioned
above, the parasites may also cause lesions in less
common sites: the lymph nodes; the skin of the perineal
region; the uterine cervix; and the penis.
1. Amoebae in the lymph nodes (Figs. 8.18 and 8.19)
do not cause important inflammatory reactions. If
lymphadenitis is present in cases of amoebiasis, it is
usually due to a secondary infection rather than to the
amoebae.
2. Amoebic lesions of the rectum may lead to amoebic
cutaneous perineal alterations (Figs. 8.20-8.22) which
may originate by contiguity and cause recto-cutaneous
fistulae and lesions similar to cutaneous tumoral mani-
festations This type of lesion naturally heals rapidly
when specific anti-amoebic drug treatment is applied.
Making a differential diagnosis between cutaneous
amoebiasis and Meleney's synergistic gangrene is
discussed in reference 17.
3. Sometimes, we have come across amoebic lesions at
the exocervix (Figs 8.23 and 8.24) which resemble
cauliflower-like growths and are virtually impossible
to differentiate from cervical carcinomas. If, in regions
endemic to amoebiasis, these exocervix lesions are
seen with extensive necrotic areas and carcinomatous
cells are not immediately found, it is recommended
that amoebae are looked for using the special staining
methods. Amoebae may be found in routine Papanic-
olaou smears: in one case, in a patient wearing an
PROTOZOAN DISEASES 47

Fig. 8.11 Multiple hepatic abscesses due to amoebic infection in a 4- Fig.8.12 The histological picture of a liver 'abscess' of the case shown
month-old infant in Figure 8,11, Parasites are not seen at this magnification and staining
method, H&E

Fig. 8.14 The pro-

tuberance seen in the
skin of the right-hand
upper quadrant of the
abdomen is produced
by an amoebic liver
abscess

Fig.8.13 'Reactive hepatitis' with hepatomegaly in an amoebic infec-

tion, Numerous mitoses of hepatocytes are seen, but never amoebae.
H&E

Fig. 8,16 This surgical specimen is the resected lung abscess of Fig
8,15

Fig. 8.15 Amoebic abscess in the lower lobule of the right lung
48 PROTOZOAN DISEASES

,
•

Fig.8.17 Amoebic brain abscess. The central nervous system is very Fig.8.18 Two structures are seen in the marginal sinus of a mesenteric
rarely attacked by Entamoeba histolvtica lymph node which represent amoebae. This organ is rarely invaded by
amoebae. H&E

Fig.8.19 The same lymph node as in Fig. 8.18 with parasites positive Fig. 8.20 Amoebae were found in the biopsy of this extensively
in this staining method. Grocott ulcerated perineal region. Cutaneous carcinoma had been the clinical
diagnosis previously

Fig. 8.21 The same case as in Fig. 8.20 three months after specific Fig.8.22 Histology of the case of Fig. 8.20. Numerous organisms of
treatment Entamoeba histo1vtica are seen. H&E
PROTOZOAN DISEASES
intrauterine contraceptive device 18 , and, in another, in
association with a cervical squamous cell carcinoma 1B
Amoebic infections of the uterine cervix without mucosal
defects are an exception.
4. Amoebic lesions of the penis (Fig. 8.25) are rare and
originate only from sexual relations with an infected
individual.
Histopathology In order to obtain good results in the
diagnosis of the amoebae, it is indispensable to have
personal experience. Personnel who have no appropriate
training and do not examine this sort of specimen daily
run the risk of making too many false positive diagnoses.
Histological diagnosis of amoebiasis may be difficult 20
Figs. 8.26-8.28 show intestinal lesions at low power.
The trophozoites of E. histoJytica can be seen in the
intestinal content and in the tissues of the intestinal wall
at various stages of preservation. If the results of the H&E
or iron haematoxylin staining methods are not satisfactory,
the PAS and Grocott methods give good results and bring
the parasites out clearly, above all incases with few
parasites and in slides with badly preserved ones. Often,
amoebae contain red blood cells, a phenomenon called
erythrophagia (Fig. 8.2a). Occasionally, numerous amoe-
bae are situated in the lumen of blood or lymphatic vessels,
without signs of vasculitis (Fig. 8.29). Sometimes, it
is difficult to distinguish amoebae from macrophages or
ganglion cells (Fig. 8.30). The problem of differential
diagnosis of the different species of amoebae may arise
in smears of the intestinal content but does not exist in
tissue sections since only E. histoJytica is found in tissues
The amoebae may be present in the cavities of
abscesses, in the liver or in other viscera, but. more often,
they perish and disappear before being recognized by the
pathologist. However, amoebae are more likely to be
encountered in the granulation tissue on the periphery of
an abscess Nevertheless, in spite of the use of special
staining methods, false negative diagnoses are also poss-
ible when pus of liver abscess is obtained by puncture.
Recently, we have achieved good diagnostic results by
examining sections of cell blocks of this material stained
with the PAS method. I n these sections, only a few
necrobiotic amoebae, difficult to recognize as such, were
detected with the H&E stain but they came out clearly
with the PAS method (Fig. 8.31)
The tissue reaction consists mainly of Iympho-histi-
ocytic infiltrates; occasionally eosinophilic leukocytes are
present. Neutrophilic leukocytes and fibrine exudation are
scarce or absent and, when they are present. are due to
a secondary associated bacterial infection.
In the liver, the so-called abscesses are not true ones
because their content consists of semiliquid necrotic
material without leukocytes. The above mentioned reac-
tive hepatitis, present in the hepatomegaly of amoebic
colitis, shows infiltrates of Iympho-histiocytes and a
certain number of granulocytes in the hepatic sinus
and in periportal spaces. Also, a marked oedema and,
9. ACANTHAMOEBIASIS
Introduction
Free-living 'soil' or 'water' amoebae may cause severe
diseases of the central nervous system with meningitis or
meningo-encephalitis. Species of the genus NaegJeria
cause primary amoebic meningo-encephalitis (PAME),
while Acanthamoeba species cause chronic granuloma-
tous amoebic encephalitis (GAE). Keratitis due to acan-
thamoebae has also been observed l - 5 . Naeg/eria is not an
acanthamoeba. Acanthamoebiases are really 'infections
due to free-living amoebae'.
I n the world literature, no more than 200 cases have
49
occasionally, numerous hepatocytes showing mitoses can
be observed.
'Amoebic granulomas' have been mentioned above
when 'amoebomas' were discussed. It must be empha-
sized that the terms granulomas or granulomatous reac-
tions refer to histological features. Neither granulomas nor
granulomatous reactions are found in amoebic infections.
References
1. Miller, M. J., Matthews, W. H. and Moore, D. F. (1968). Amebiasis
in Northern Saskatchewan. Can. Med. Assoc. J, 99, 696
2. Rolfini, R. G. (1965) Enterocolitis grave en el material aut6psico de
Merida. Tesis doctoral U niversidad de Los Andes, Merida/Venezuela
3. Liscano, T. R. de (1978). Amibiasis. Revisi6n del Material Anatomo-
Patol6glco de Merida. Trabajo de Ascenso, Fac. de Medicina, ULA.
Merida/Venezuela
4. Rigothier. M. C., Vuong. P. N. and Gayral. P (1989). A new
experimental model of cecal amebiasis in rats. Ann. Parasitol. Hum.
Camp., 64, 185
5. Becker, I.. Perez Tamayo, R.. Montfort, I., Alvizouri, A M, Perez
and Montfort. R. (1988). Entamoeba histolytlca role of amebic
proteinases and polymorphonuclear leukocytes in acute experimen-
tal amebiasis in the rat. Exp. Parasito!.. 67, 268
6. Chadee, K. and Meerovitch. E. (1989). Entamoeba histolytica:
diffuse liver inflammation in gerbils (Meriones unguiculatus) with
experimentally induced amebic liver abscess. J Protozool., 36, 154
7. Yu, Y. and Lian, W. N. (1991). Histopathology of experimental
hepatic amebiasis. Chung-Kuo, 9, 35
8. Koppats, K. et al. (1990). Colitis ulcerosa oder Amoebenkolitis-ein
kasuistischer Bericht. Z. Ges. Inn. Med., 45, 25
9. Mironov, N. A and Soskin. la M. (1990). A fatal case of amebic
dysentery (Russ.). Med. Parazitol. Mask.. 58, 9
10. Hossain, A, Bolbol, A S, Chowdhury, M. N. and Bakir, T M.
(1989). Indirect haemagglutination (IHA) test in the serodiagnosis
of amoebiasis. J Hyg. Epidemiol. Microbiol. Immunol., 33, 91
11. Salfelder, K. (1961) Ueber eine kontrastreiche Anfarbung von
Entamoeba histolytica im Gewebe. Z. Tropenmed. Parasit, 12, 273
12. Brown. M. etal. (1991). Detection of HIV-l in Entamoeba histoly-
tica without evidence of transmission to human cells. AIDS, 593
13. Nadler, S el al. (1990). Appendiceal infection by Entamoeba
histolytlca and Strongyloides sterocoralis presenting like acute
appendicitis Dig Dis. Sci.. 35, 603
14. Spencer, H. (ed) (1973) Tropical Pathology Handb. Spez. Path.
Anat. Bd. 8. Springer Verlag
15. Trautmann, M. el al. (1990). Multiple Ambbenleberabszesse
sonographische Diagnostik und ultraschallgezielte Punktion. Ultra-
schall Med, 11, 142
16. Disko, R. and Schinkel, T. (1979). Zur Diagnose des Ambben-
Leberabszesses. Elne Stu die an 107 Fallen. Munch Med. Wschr..
121,1536
17. Davson, J .. Jones. D. M. and Turner. L. (1988). Diagnosis of
Meleney's synergistiC gangrene. Br. J Surg.. 75, 267
18. Arroyo. G. and Quinn, J. A Jr. (1989). Association of amoebae
and actinomyces in an intrauterine contraceptive device user. Acta
Cytol.. 33. 298
19. Arroyo, G. and Elgueta, R. (1989). Squamous cell carcinoma
associated with cervicitis. Report of a case. Acta Cytol.. 33. 301
20. Konstantinov. G. S. and Blokhin. A V. (1988). The morphology of
amebiasis. Arkh. Patol., 50, 44
been recorded, mostly in small groups of children or
adolescents. They have been found in Australia and New
Zealand, in European countries, in the USA and single
cases have been observed elsewhere. I n Venezuela, we
know of three reported cases 67
Spontaneous acanthamoebiasis, to our knowledge, has
been reported only exceptionally in lower animals 8
Experimentally, amoebic infections of this kind may be
produced by various routes in mice, rabbits and monkeys.
Rhinitis, encephalitis and pneumonia (after direct inocul-
ation) have been achieved in these animals 9- 11 .
 50 PROTOZOAN DISEASES

Fig. 8.23 Amoebic cervicitis. Parasites are not seen at this mag-
nification and with this staining method. H&E

Fig.8.26 Low power view of early amoebic colitis. H&E

Fig. 8.24 Higher power of Fig. 8.23. A nest of amoebae may be

recognized easily in this field. H &E

Fig. 8.27 Early circumscribed necrosis of the mucosa of the large

intestine due to infection with amoebae. Parasites are not seen at this
magnification. H&E

Fig. 8.25 Amoebic lesions of the penis with extensive ulceration and
haemorrhages
PROTOZOAN DISEASES 51

Fig. 8.28 Early lesion of amoebic colitis with an abscess at a crypt. Fig. 8.29 Numerous amoebae present in the lumen of a vein in the
The leukocytic exudate is probably due to secondary bacterial infection. submucosa of the large intestine. The wall of the vein is intact. H&E
H&E

•
•
•
)

Fig.8.30 Entamoeba histolvtica seen in tissues with the routine stain. Fig. 8.31 Amoebae in section of a cell block from contents of a liver
H&E abscess are seen clearly with this staining method. PAS
52
The disease produced by Naegleria species (PAME) is
reported with increased frequency after swimming in
pools, lakes and rivers. This form shows an acute fulminat-
ing course and is always fatal. In addition, PAME occurs
more frequently than GAE.
The amoebic infection caused by Acanthamoeba
species, on the other hand, occurs as an opportunistic
infection 12 in clinically ill or immunosuppressed patients
and without contact with water. It has been reported
in AIDS patients 13 .14 and has a more chronic course
but nevertheless, a fatal outcome.
Clinical diagnosis of this disease is made by detecting
trophozoites in the spinal fluid (Fig. 9.1) by culture of
spinal fluid or tissue specimens of the brain in the
NNN medium. Immunofluorescence techniques and the
complement fixation test are performed in special research
laboratories.
The parasite
The important pathogenic species for man and mouse are
Naegleria fowleri, Naegleria australiensis, Acanthamoeba
castellanii and Acanthamoeba culbertsoni. The terms
Limax and Hartmanella as genera are now obsolete. Non-
pathogenic species of soil or water amoebae do exist but
will not be described here in detail.
The Naegleria and Acanthamoeba species measure
between 10 and 40 jlm. The former are somewhat smaller,
about 7-22 jlm, and the latter. 15-45 jlm. Trophozoites
and cysts may be distinguished. Trophozoites are seen in
tissues. They are spherically shaped and almost always
possess only one nucleus, but exceptionally, up to three
may be present. They stain with H&E. iron haematoxylin
and trichromic methods and are PAS- and Grocott-
negative, In spinal fluid, trophozoites measure 8-10 jlm
and are motile.
Cysts (persistent forms) of these amoebae are found
ubiquitously, e,g. in dust water and in the upper respira-
tory tract of man 15- 18 They are uninuclear and have a
thick membrane which may be irregular. Acanthamoeba
cysts may show stellate or polyhedral structures; they
have been described in tissues by Garcia Tamayo et al 7
In the presence of bacteria, amoebae may be cultured
easily in Nelson medium and also in Bacto agar Difco in
horse serum, Axenic cultures have been achieved too, In
tissue cultures. soil amoebae have a typical cytopathic
effect. In plate cultures Naegleria species have 2 flagella
Pathogenesis
In Naegleria infections, the portal of entry of the parasites
is probably the nasal mucosa, Here an inflammatory
process develops, The amoebae penetrate the mucosa
and migrate along blood vessels and nerve fibres (N
olfactorius) centripetally, through the cribriform plate of
the ethmoid into the subarachnoid space and, from there,
into the brain, This movement of amoebae has been
shown experimentally after intranasal administration of
cu Itu re material 19 .
By haematogenous dissemination. the amoebae, appar-
ently, reach internal organs and may cause inflammatory
processes. However. the parasites soon perish in these
viscera and have not been confirmed at these sites.
Involvement of lung, kidney, liver, pancreas. lymph nodes
and myometrium has been described but without the
presence of parasites in these viscera.
Acanthamoeba species may use the upper respiratory
tract as portal of entry. The CNS is probably secondarily
affected from another active focus, e.g, the lungs or the
skin 20
PROTOZOAN DISEASES
Pathology
Meninges and brain are affected by species of Naegleria,
and the brain (occasionally also the meninges) by Acan-
thamoeba species, Further. the cornea may be involved.
In human beings, lesions produced by these species of
amoebae have been reported in liver, lungs, kidneys,
pancreas, lymph nodes and myometrium. but the parasites
themselves have not been described in internal organs
outside of the CNS (possibly they perish soon after
haematogenous dissemination).
Grossly, the purulent and haemorrhagic necrotizing
meningitis and the purulent foci in cortical and subcortical
areas of the brain, as well as the keratitis, do not present
special or specific features, They may be easily confused
with the suppurative meningitis or necrotizing haemor-
rhagic encephalitis of any other aetiology, Specific gross
lesions of internal organs are not known. Circumscribed
tumour-like lesions have been observed in the brain in
the GAE form of the disease 21 .
Histologically, we have seen, personally, only three
cases. one from Venezuela. one from Czechoslovakia and
one from the USA all of the PAM E variety, The amoebae in
the tissues of these cases were almost solely trophozoites.
Only a few large parasites seemed to be cysts, some with
thin membranes and others with thicker and irregular
membranes. Garcia Tamayo et a/. have illustrated cysts in
tissues in an Acanthamoeba infection 7 On an average,
the amoebae measured 10 jlm and were of a spherical
shape, or occasionally amoeboid or polyhedral. The
majority of amoebae had one small nucleus, centrally
located; only few amoebae had several nuclei. but no
more than three nuclei could be seen in one amoeba.
Often, the cytoplasm of the amoebae was clear, similar
to a vacuole, but inhomogeneous or granular inclusions
were also seen in variable amounts in the cytoplasm. The
amoebae in these cases stained weakly with the H&E,
iron haematoxylin and the Goldner stain (Fig. 9.2) but
did not stain at all with the PAS or Grocott methods. Often,
large nests of numerous amoebae showed necrobiotic
changes of the amoebae themselves. Figs. 9.3-9,5 show
brain tissue with soil amoebae at low power, Figs, 9.6
and 9.7 at medium power and Figs. 9.8-9.10 at high
power with the H&E stain.
The parasites were mostly located. often in clusters
with numerous amoebae. in perivascular clear spaces
or in nests, localized in the parenchyma without any
alterations or showing clear spaces, This means that there
is focal destruction of brain tissue. Frequently, the walls
of large blood vessels were invaded by amoebae. Often.
parasites situated in dense cell infiltrates, e.g. granulo-
cytes, were recognized only with difficulty. They were
seen clearly inside nerve cells (neuronophagy) (Fig,
9.9), a feature which previously had been erroneously
interpreted by us as phagocytosis (amoebae engulfed by
macrophages). Tissue reaction in these cases consisted
of oedema, coli iquative necrosis, exudation of fibri n
and extensive cellular infiltrates with a predominance of
neutrophilic leukocytes. Often, the latter were densely
packed with necrobiosis of these cells, i.e. a real suppura-
tive lesion was present. In addition, thromboses of small
and medium blood vessels and extensive haemorrhages
were observed, Perivascular infiltrates with granulocytes,
lymphocytes and plasma cells were found in the paren-
chyma, without amoebae. In some areas, a marked prolif-
eration of astrocytes was noted.
A granulomatous reaction with giant cells was
described in the GAE form 22 - 24 We have not seen lesions
of this kind personally.
Histological differential diagnosis of amoebae is rela-
tively easy. In tissues, intestinal amoebae (Entamoeba
PROTOZOAN DISEASES 53

Fig. 9.1 Naegleria fowleri in smear of spinal fluid. H&E Fig . 9.2 Clusters of soil amoebae in brain. Goldner

Fig. 9.3 Low power view of brain tissue with numerous clusters of
soil amoebae. H&E
54 PROTOZOAN DISEASES

Fig. 9.4 Numerous soil amoebae in brain tissue with inflammation. Fig.9.5 Acanthamoebiasis. In addition to parasites. marked leukocytic
H&E inflammation is seen. H&E

Fig. 9.6 Nest of soil amoebae in necrotic brain tissue. H &E Fig.9.7 Cluster of soil amoebae in a perivascular space. H&E
PROTOZOAN DISEASES 55

Fig.9.8 Soil amoebae in brain tissue at high magnification. H&E

Fig. 9.9 'Soil amoeba' in the brain are phagocytising nerve cells
(neurophagy). H&E
56
histolytica) are pleomorphic, show erythrophagia and
stain with PAS and weakly with Grocott. In addition, the
purulent tissue reaction in acanthamoebiasis is not found
in the lesions produced by E. histolytica.
References
1. Witschel, H., Sundmacher, R. and Seitz, H. M. (1984). Amoeben-
Keratitis. Ein klinisch-histopatologischer Fallbericht. K/in. Mb/.
Augenheilk., 185, 46
2. Florakis, G. J., Folberg, R., Krachmer, J. H., Tse, D. T., Roussel. T.
J. and Vrabec, M. P (1988). Elevated corneal epithelial lines in
Acanthamoeba keratitis. Arch. Ophthalmo/., 106, 1202
3. Wilhelmus, K. R, McCulloch, R. R. and Osato, M. S (1988).
Photomicrography of Acanthamoeba cysts in human cornea. Am.
J. Ophtha/mo/., 106, 628
4. Karayianis, S. L, Genack, L. J .. Lundergan, M. K. and Schumann.
G. B. (1988). Cytologic diagnosis of acanthamoebic keratitis. Acta
Cyto/., 32, 491
5. Beattie, A. M. et aJ. (1990). Acanthamoeba keratitis with two species
of Acanthamoeba. Can. J. Opatha/mo/., 25, 260
6. Brass, K. (1973). Meningo-encefalitis amebiasica primaria (por
Naegleriasis). Arch. Venez. Med. Trap., 5, 291
7. Garcia Tamayo, J., Gonzalez, J. E. and Martinez, A. J. (1980).
Meningoencefalitis amibiana primaria y encefalitis granulomatosa
amibiana. Rev. Med. Venez., 27, 84
8. Ayers, K. N, Billups, L. H. and Garner, F. M. (1972). Acanthamebi-
as is in a dog. Vet. Patho/., 9, 221
9. Culbertson, C. G., Smith, J. W., Cohen, H. K. and Minner, J. R.
(1969). Experimental infection of mice and monkeys by acantha-
moeba. Am. J. Path., 35, 185
10. Martinez, A. J., Duma, R. R., Nelson, E. C and Moretta, F. L.
(1973). Experimental Naegleria meningoencephalitis in mice. Lab.
Invest. 29, 121
11. Willaert. E. and Stevens, A. R. (1980). Experimental pneumonitis
induced by Naegleria fowleri in mice. Trans. R. Soc. Trop. Med.
10. BLASTOCYSTIS INFECTION
Introduction
Blastocystis hominis was accepted, previously, as an
intestinal yeast. harmless for humans 1 . From the sixties
on, it was considered a protozoan 2 and, now, its patho-
genicity for man is being discussed 3.4 It has been found
worldwide with an average prevalence of 10-15% in
people with enteric symptoms; also in Venezuela 5.
Whether Blastocystis hominis occurs naturally in lower
animals we do not know. Experimentally, diarrhoea may
be produced in guinea pigs and non-human primates 6
when these species are infected with B. hominis.
Enterocolitic symptoms, flatulence, diarrhoea, abdomi-
nal cramps and pain as well as anorexia, are thought to
be caused by this parasite. Clinical diagnosis may be
made by examining fresh stools prepared with physiologi-
cal saline and seen with the light or phase-contrast
microscope. However, a single examination of a stool is
not sufficient. When, in stools with neutrophilic leuko-
cytes, pathogens are not found, B. hominis should be
looked for.
The parasite
Blastocystis hominis, known since the beginning of this
century as a yeast. has been considered a protozoan,
belonging to the Sporozoa, since 1967. The vacuolated
cell is spherical in shape and, characteristically, shows a
large central vacuole which occupies 75% of the cell
volume and is surrounded by a narrow rim of cytoplasm
containing nuclei and some inclusions. It has a signet
ring appearance (Fig. 10.1). Commonly, there is one
nucleus situated in the peripherical membranous-like
structure but. occasionally, there are 2-4 nuclei. Mito-
chondria are confined to the thin peripheral band of
PROTOZOAN DISEASES
Hyg.. 74, 779
12. Harwood, C R, Rich, G. E.. McAleer, R. and Cherian, G. (1988)
Isolation of Acanthamoeba from a cerebral abscess. Med. J. Aust..
148, 47
13. Martinez, A. J. and Janitschke, K. (1985). Acanthamoeba, an
opportunistic micro-organism. A review. Infections, 35, 251
14. Anzil, A. P et aJ. (1991). Amebic meningoencephalitis in a patient
with AI DS caused by a newly recognized opportunistic pathogen.
Leptomyxid ameba. Arch. Patho/' Lab. Med.. 115, 21
15. Michel. R. and De Jonckheere, J. F. (1983). Isolation and identifi-
cation of pathogenic Naegleria australiensis (De Jonckheere 1981)
from pond water in India. Trans. R. Soc. Trap. Med. Hyg.. 77, 878
16. Kadlec, V .. Skvarovil, J .. Cerva. L. and Nebilznivil, D. (1980).
Virulent Naegleria fowleri in indoor swimming pool. Folia Parasito/.
Prag., 27, 11
17. Michel. R. and Just. H. M. (1984). Acanthamoeben, Naeglerien
und andere freilebende Amoeben in Kuhl- und Spulwasser von
Zahnbehandlungseinheiten. Zb/. Bah J. Abt Orig. B .. 179. 56
18. Michel, R., Roehl. R. and Schneider, H. (1982). Isolierung von
freilebenden Amoeben durch Gewinnung von Nasenschleimhaut-
abstrichen bei gesunden Probanden. Zb/. Bakt I Abt. Orig. B .. 176,
155
19. Culbertson, C. G. (1971). The pathogenicity of soil amebas. Ann.
Rev. Microbia/" 25, 231
20. Martinez, A. J. (1991). Infection of the central nervous system due
to Acanthamoeba. Rev. Infect. Dis.. 13, Suppl. 5. 399
21. Kwame Ofori-Kwakye et aJ. (1986). Granulomatous brain tumour
caused by Acanthamoeba. J. Neurosurg., 64, 505
22. Patras, D. and Andujar, J. J. (1966). Meningoencephalitis due to
Hartmanella (Acanthamoeba). Am. J. Clin. Path .. 44, 226
23. Robert. V. B. and Rorke. L. B. (1973) Primary amebic encephalitis
probably from Acanthamoeba. Ann. Int. Med., 79, 174
24. Matson, D.O., Rouah, E, Lee, R. T., Armstrong, D., Parke, J.
T. and Baker, C. J. (1988). Acanthameba meningoencephalitis
masquerading as neurocysticercosis. Pediatr. Infect Dis. J., 7, 121
cytoplasm between the membrane surrounding the vol-
uminous inner body and the outer membrane 7 .8 There are
wide variations in size. Blastocystis hominis may measure
from 5-12011m in diameter. This parasite reproduces
rapidly in human serum as culture medium.
In cultures, three morphological forms may be observed:
vacuolic, amoeba-like with pseudopodes, and granular.
In faecal specimens, the vacuolated and amoeba-like
forms are found.
Parasites may be stained permanently with iron haema-
toxylin (Fig. 10.2), Goldner or the Giemsa method; with
the last. they stain weakly. The parasites are Ziehl-
Nielsen-, Gram- and Grocott-negative. Their vacuoles do
not stain with Lugol. At Merida, we have achieved good
results by staining sections of cell blocks (Figs. 10.3 and
10.4). Reproduction of parasites takes place by binary
fission or sporulation.
Pathogenesis
The mechan isms of the pathogenic actions of th is parasite
have not been elucidated. Massive infections with Blasto-
cystis hominis may lead to enterocol itic symptoms.
Whether this is due to the parasite alone or to the
interaction of Blastocystis hominis with other organisms
has yet to be resolved.
Invasion of tissues by this parasite has not been
confirmed convincingly. In one case, a human death due
to these organisms was reported because evidence of
mucosal invasion of the colon was shown postmortem 9 .
Pathology
Parasites are found in the lower ileum and caecum.
Descriptions of gross or microscopic lesions do not exist
PROTOZOAN DISEASES 57

Fig . 10.1 Blastocvstis hominis cell in smear of faeces. Note the cyst Fig. 10.2 Blastocvstis hominis cel ls in smear of faeces. Iron-haema-
like appearance with the nucleus in the 'cyst wall'. Iron- haematoxylin toxylin

Fig. 10.3 Blastocystis homims cells in section of cell block of faecal Fig.10.4 High magnifi cat ion of Fig. 10.3
material. Iron-haematoxylin
 58 PROTOZOAN DISEASES

Fig.10.5 Numerous Blastocystis hominis organisms on the surface of Fig.10.6 Same case as Fig. 10.5. PAS
the necrotic mucosa of the large bowel. Diffuse pseudomembranous
colitis post surgery of carcinoma of the oesophagus. (Case of Dr J.
Boehm, Mlinchen, Germany). Low power. H&E

Fig.10,7 Same case as Figs. 10.5 and 10.6. Nuclei are situated in the Fig. 10.8 Same case as Figs. 10.5-10.7. High power. Iron-haema-
peripherical annular-like cytoplasm. This signet-ring appearance cannot toxylin
be seen. High power. H&E
PROTOZOAN DISEASES
in the literature. While some reports stress the potential
pathogenicity of Blastocystis hominis 4.1O , there are others
who deny that this parasite has a pathogenic role n
Recently, an autopsy case was kindly provided from
Germany, showing numerous organisms of Blastocystis
hominis, arranged colony-like and attached to the surface
of the large bowel, apparently as secondary non-invasive
opportunistic infection in an immunodeficient patient
(Figs. 10.5-10.8).
Blastocystis hominis is the most important source of
error in stool examinations for protozoa. These parasites
may be confused easily with cryptosporidians or intestinal
amoebae.
References
1. Brumpt. E. (1912). Blastocystis hominis n. p. et formes voisines.
Bull. Soc. Pathol. Exot., 5, 725
2. Zierdt. C. H. et al. (1967). Protozoan characteristics of Blastocystis
hominis. Am. J. Clin. Patho/" 48, 495
3. Zierdt. C. H. (1983). Blastocystis hominis, a protozoan parasite and
11. TOXOPLASMOSIS
Introduction
Toxoplasmosis is an important infectious disease. I nfec-
tion with Toxoplasma gondii is, worldwide, of a high
prevalence. Latent symptomless infections are far more
frequent than disease. Symptomatic disease, on the other
hand, is rare but may be severe in man. Today, this is one
of the prominent opportunistic infections in immuno-
deficient persons and typical in AI OS patients l - 5 . The
proportion of infected persons is progressively higher in
older age groups. More than 80% of the adult rural popula-
tion in Venezuela 6 was found to have positive serology
to T. gondii.
The cat (Felis domestica) is the specific definitive host
for Toxoplasma gondii 7- 10 , although almost all mammals
are non-specific intermediate hosts 11 .12 In dogs, lately,
toxoplasma-like cyst-forming sporozoans which could
not be identified have been reported in nervous tissue 1314
Mice and other animal species may be used for experimen-
tal purposes 1516 .
There are two principal clinical forms of toxoplasmosis:
1. An extrauterine infection acquired in a natural way.
Opportunistic infections with disseminated disease,
lymphadenitis and ophthalmitis are of special interest
in this group.
2. An intrauterine toxoplasmotic infection in a pregnant
woman and the transplacental infection of the fetus.
Clinical diagnosis is only confirmed by the demonstration
of the parasite or specific antibodies. Microscopically, the
toxoplasmas may be found in the spinal fluid, body and
organ fluids as well as organs. Inoculation of specially
sensitive Toxoplasma-free white mice and special rats
may be used for diagnostic purposes.
The parasite
Toxoplasma gondii is the most important of the four
coccidian species; the other three are Sarcocystis bovi-
hominis, Sarcocystis suihominis (Section 13, Sarcos-
poridiosis) and Isospora belli (Section 14, Isosporosis).
The Coccidia belong, together with the Plasmodia, to
the class of Sporozoa.
It goes through a heteroxenous cycle of evolution, i.e.
with several hosts. The final host is solely the cat which
becomes contaminated after eating infected mice. In the
feline digestive tract the three phases of the coccidian
59
intestinal pathogen of human beings. Clin. BioI. Newsleu., 5, 57
4. Zierdt. C. H. (1991). Blastocystis hominis- past and future. Clin.
Microbial. Rev., 4. 61
5. Tirado Castrillo. de A. et al. (1989). Frecuencia de infecci6n par
Blastocystis hom in is: un ano de estudio. IV Congreso Panamer.
Infect. Caracas, Febrero 1989
6. McClure, H. M. et al. (1986). Blastocystis hominis in pig-tailed
macaque, a potential enteric pathogen for nonhuman primates. Lab.
Anim. Sci., 30, 890
7. Zierdt. C. H. et al. (1988). Biochemical and ultrastructural study of
Blatocystis hominis. J. Clin. Microbial., 26, 965
8. Matsumoto, Y. et al. (1987). Light-microscopical appearance and
ultrastructure of Blastocystis hominis. an intestinal parasite of man.
Zbl. Bakt Mikrobiol. HVg. A, 264, 379
9. Zierdt. C. H. and Tan, H, K. (1976). Ultrastructure and light
microscope appearance of Blastocystis hominis in a patient with
enteric disease. Z Parasitenkd, 50, 277
10, Sheehan, D, J, et al. (1986), Association of Blastocystis hominis
and symptoms of human disease, J. Clin. Microbia/" 24, 548
11, Markell, E. K, and Udkow, M, p, (1986), Blastocystis hominis:
Pathogen or fellow traveller. Am. J. Trop, Med. HVg, , 35, 1028
cycle take place and end with the expulsion of oocysts.
After sporulation outside the animals, new infections of
mice, domestic animals, e.g, sheep etc, and cats occur.
Table 3 shows the cycle of evolution.
The parasite has a half-moon form or is sickle-shaped.
It measures 2-5/!m when observed in liquid smears
and fresh histological preparations, above all as single
organism. However, when seen in clusters intracellularly,
i,e. in cysts or pseudocysts, they always appear as spheri-
cal elements in tissue sections, This is of practical import-
ance because the observer, in order to make a diagnosis,
should not look for sickle-shaped structures in tissue
sections (Figs, 11.1-11.5), When the parasites reproduce
inside tissue cells (muscular, glial or endothelial cells and
in macrophages), they form numerous young parasites
which fill the cell, pushing cytoplasm and other elements
to the periphery, thus forming the already mentioned
pseudocysts, Two types of Toxoplasma are distinguished
by their manner of multiplication: the tachyzoites in
pseudocysts, in the acute phase of the disease; and the
bradyzoites in cysts with membranes, in the chronic form.
However, these two types do not always show visible
structural differences, Both types may appear in nests,
but the bradyzoites tend to do this more often because
they frequently present as cysts which are PAS-positive.
This PAS-positivity seems to be related to the storage of
glycopolysaccharides,
Artificial culture media which induce growth and multi-
plication of Toxoplasma gondii are not known; however,
they may be kept alive in tissue cultures, These parasites
can also be preserved in a viable condition for many
months by adding glycerol or OMSO and then deep
freezing in liquid nitrogen 17
Pathogenesis
1, The extrauterine and acquired natural infection occurs
in two ways:
a) Raw meat (pigs, sheep or cows) harbouring para-
sitic cysts may be eaten.
b) Oocysts or sporocysts of Toxoplasma gondii stem-
ming from faeces of a cat may reach the human
digestive tract (Oocysts are highly resistant and
may remain viable for longer than a yeaL)
From the human gut haematogenous dissemi-
nation takes place, The musculature and the central
60 PROTOZOAN DISEASES

Fig.11.1 Toxoplasma gondiiin smearof human bone marrow showing Fig. 11.2 Suspected toxoplasms in smear of pleural exudate. later
half-moon-shaped parasites. Giemsa determined as contaminating fungus cells: here shown as differential
diagnostic elements. Giemsa

Fig. 11.3 Cyst and pseudocyst with Toxoplasma gondii parasites. The Fig. 11.4 Toxoplasmic cyst without inflammatory reaction at high
densely packed organisms are located in a cyst (dark) and the scarce power in the brain. H&E
parasites in a pseudocyst. Section of a toxoplasmic encephalitis. H &E

Fig. 11.5 Single. extracystic toxoplasms in tissue section of brain. Fig. 11 .6 Piringer-Kuchinka lymphadenitis. Cell nodules of variable
H&E sizes made up of histiocytes. reticular and epithelioid cells. Parasites of
Toxoplasma gondii are found only occasionally in this kind of lesion.
H&E
PROTOZOAN DISEASES 61

Table 3 The evolutionary cycle of Toxoplasma gondii (G. Piekarski. Medical Parasitology. 1989)

5 6
Schizogony Gamogony

Cysts
(Musculature. CNS)
with cystozoites
(' bradyzol tes ')

7
Sporogony

~
Merozoltes
(tachyzoites)

(1
~ Mouse
I@ Man

e
Pig

~ Sheep l>
Cow
®
3 @ Intrauterine infection

Pseudocysts

Intr acellular multiplication

by endodyogeny

A Cats. the specific defi nitive hosts. excrete Toxoplasma gondii oocysts
in their faeces (1). Almost all mammals (non -specific intermediate
hosts) can be infected B by the sporocysts (each with four
sporozoites. 2).
B For example. mouse B,. pig. sheep. cow B2 • and man B3
The parasites multiply intracellularly asexually (acute phase) (3)
and form cysts (chronic phase) (4). These lead to renewed infection
in meat eaters. After a cat is infected. the organisms first multiply
asexually in the small intestinal epithelium (schizogony 5).
Thereafter. they form gamontes and gametes (gamogony. 6). Devel-
opment of oocysts and sporocysts. each containing four sporozoites
(sporogony. 7). occurs after fertilization.
C Intrauterine infection; congenital toxoplasmosis
Infection pathway in man B3:
a. Through oral ingestion of sporulated oocysts (2)
b. Consumption of raw cyst-containing meat from sheep. pig or
cow
c. Intrauterine transmission

nervous system are the favoured sites of lesions (tropism).
The incubation period is 2-3 weeks. The fact that. all
over the world. the prevalence of serologically positive
reactions is so high and yet the number of clinical
symptomless cases is so low indicates that there must be
numerous asymptomatic or subclinical latent infections.
2. If the infected person (see 1) is a woman who is preg -
nant at the time of the first infection with T. gondii.
she may miscarry or transmit the parasite through the
placenta to the fetus with resulting congenital ~better
described as connatal or prenatal) toxoplasmosis 1 -20. In
this situation. the Toxoplasma gondii infection seems to
be more virulent than when the infection is through the
digestive tract. Transplacentally-induced toxoplasmosis
has also been detected in fetal pigs 21 .

62
3. Indirect transmission, for example through flies or
other insects contaminating food with oocysts, does
occur but is in practice of minor importance.
Pathology
The musculature, central nervous system and eyes 22 and
lymph nodes 23 .24 are the favoured sites of involvement. In
cases of disseminated toxoplasmosis, mostly the lungs,
liver and adrenal glands are involved. In massive infec-
tions, all organs may show lesions.
Natural acquired infection. It is rarely that this
infection is followed by an acute or chronic course and
fatal cases are even more rare. Gross lesions are of
an entirely non-specific nature. It seems appropriate
to discuss in this context toxoplasmotic lymphadenitis,
toxoplasmotic ophthalmitis and toxoplasmosis due to
opportunistic infection.
Lymphadenitis. In adolescents and young adults,
toxoplasmotic lymphadenitis appears predominantly in
the rear cervical region, or manifests itself as generalized
lymphadenopathy. The histological lesions, first described
by Piringer-Kuchinka in 1958, have been confirmed by
other observers 25 . They are characteristic but not specific
for infection with Toxoplasma gondii.
Isolated multiple histiocytes or nodules of histiocytic
cells. similar to reticular or epithelioid cells, are found. In
the cell nodules, neither necrosis nor giant cells are
observed (Fig. 11.6), and they do not have the features
of true granulomas. Proliferation of this sort of cell and
the formation of cell nodules are also seen in Hodgkin
disease, infectious mononucleosis and in Whipple dis-
ease. The described histological lesions should be con-
firmed by a positive serological test. Parasites are rarely
seen in the lymph node lesions of th is aetiology; therefore,
definitive aetiological diagnosis should be based on the
histological lesions, together with positive results of the
serological test.
Ophthalmitis. If toxoplasmotic aetiology has been
established, there is a possibility that this is the late
consequence of a neonatal infection, or it may be due to
haematogenous infection. In toxoplasmotic ophthalmitis,
the choroid may present non-specific or necrotizing
inflammation, or, less frequently, granulomatous reac-
tions. The nests or cysts of parasites, when present. may
show necrobiotic lesions (Figs. 11.7-1110).
I n practice, there is always a problem, ina case of
chorioretinitis, in differentiating between toxoplasmotic,
histoplasmotic or tuberculous infections or diagnosing an
immunological process of undetermined aetiology. It is
estimated that a third or a quarter of all cases of chronic
ophthalmitis is due to a toxoplasmotic infection (Figs.
11.11-11.13).
Opportunistic infection. Toxoplasmosis, when an
infection of this sort is an acute form of this disease
which has, lately, been frequently observed in debilitated
patients who have suffered for a long time from various
types of chronic diseases. It has been encountered
especially in patients treated with cortisone or by irradi-
ation. in individuals with organ transplants, treated with
immunosuppression, or in persons with congenital or
acquired immunological defects, for instance AIDS. It is
thought that this sort of toxoplasmosis did not previously
exist but that Toxoplasma gondii 'made use of the oppor-
tunity' in the above-mentioned conditions to attack
without having been present earlier in man as a saprophyte
or a facultatively pathogenic micro-organism, as in
Pneumocvstis carinii. Candida sp., etc. This opportun-
istic infection by T gondii presents neither particular
nor specific pathological alterations. Furthermore, this
toxoplasmosis is not limited to the central nervous
system, as expressed in some books, but on the cont-
PROTOZOAN DISEASES
rary, is generalized (Figs. 11.14-11.21). The pathological
lesions in the brain are not very extensive, as in neo-
natal toxoplasmosis (Fig. 11.22). Often, there are other
opportunistic infections, for instance cytomegaly,
simultaneously present in one patient.
Histologically, when routine tissue sections are
reviewed, the parasites are spherical or ovoid in shape.
They may be found inside or outside cysts or pseudocysts.
We have not always been able to distinguish clearly
between these two sorts of intracellular nests of parasites.
In cysts, the organisms are densely packed and PAS-
positive. The cyst membranes are PAS-positive also.
Generally, they do not produce an inflammatory reaction.
In pseudocysts, on the contrary, organisms are less
numerous and their PAS-positivity is weak. Toxoplasma
organisms are scarce in tissues because they perish rapidly
when outside the nests and when in tissue zones where
necrobiosis is occurring. This means that the search for
single Toxoplasma organisms may be difficult and false
negative reports are frequent.
The electron microscope is superior to the light micro-
scope in the identification of Toxoplasma organisms: their
intracellular localization, type of division, lack of budding
and absence of a kinetoplast are all clearly recognizable
u Itrastructu rally.
Small yeast-like fungus cells of numerous species and
p. carinii are differentiated from Toxoplasma by their
Grocott-positivity. Protozoan organisms of other species
must be differentiated from Toxoplasma on the grounds
of their intra- or extracellular localization, presence of
kinetoplasts and situation in determined organs or tissues.
Tissue reaction does not show either typical or specific
features. Circumscribed necrotic foci, common in toxo-
plasmotic lesions, may also be observed in other acute
infections with massive generalization. In the central
nervous system, the parasites are fou nd in necrotic lesions,
in cell nodules or situated in areas of undamaged paren-
chyma. There are numerous coagulative and colliquative
necrotic foci. In the periphery of these lesions, prolifer-
ation of capillaries and a 'status spongiosus' may be seen.
Also. accumulation of foamy cells may be noted.
The glial reaction is characteristic: it consists of the
presence of gemistocytic forms of astroglia, some glial
nodules and 'naked' astroglial nuclei. The latter mimic
Alzheimer nuclei type II. and confusion may also occur
with so-called liver-glia seen in the so-called hepatogenic
encephalopathy.
Around the small blood vessels are found macrophages
(Iipophages) and focal infiltrates of scarce lymphocytes
and monocytes (Figs. 11.23-11.32). It is not clear
whether the necrotic foci are due to damage directly
produced by the parasites or whether they are the result
of circulatory disorders with hypo- or anoxaemia. The
necrotic foci in the brain later become scars and calci-
fication may also occur.
Intrauterine infection. In pregnant women, Toxo-
plasma gondii reaches the uterus after primary infection by
haematogenous dissemination and produces placentitis.
This does not occur, apparently, in women with latent
chronic toxoplasmosis. infected before the beginning of
pregnancy. If infection occurs during the first few months
of pregnancy, a miscarriage may be the consequence of
the placentitis. However, the frequency of miscarriages
due to toxoplasmotic infections is lower than was earlier
assumed. Only a minimal percentage of all miscarriages
can be attributed to infection by Toxoplasma gondii.
Furthermore, the toxoplasmotic infection has nothing to
do with so-called habitual, multiple or repeated miscar-
riages, as was believed for many years. The inflammatory
reaction in the placenta is neither marked nor characteris-
tic, and the parasites are difficult to recognize in the
infected placenta (Figs. 11.33-11.35). We, ourselves
PROTOZOAN DISEASES 63

Fig. 11.7 Toxoplasmic chorio-retinitis. Two cysts are seen without Fig.11.S Higher magnification of Fig. 11.7
inflammatory reaction in this field. H&E

Fig.11.9 Toxoplasmotic chorio-retinitis with necrobiosis and several Fig.11 .10 Toxoplasmotic chorio-retinitis with marked necrobiosis of
parasitic cysts of variable sizes. H&E cysts or pseudocysts which are hardly recognizable as such. H &E
64 PROTOZOAN DISEASES

Fig. 11.11 Toxoplasmotic ophthalmitis. Fundus of the eye with an Fig, 11.12 Toxoplasmotic ophthalmitis. Fundus of the eye with an
isolated, relatively fresh alteration and a superficial central defect advanced lesion showing a necrosis with a well-defined central ulcer

Fig. 11,13 Toxoplasmic ophthalmitis. Fundus of the eye with an Fig, 11,14 Nest of toxoplasms in a myocardial fibre without inflam-
extensive chronic lesion. Hyperaemia indicates active inflammation mation in the vicinity. Originally, this nest was confused with amastigotes
of Trypanosoma cruz; forming a pseudocyst. H&E

Fig. 11.15 Focal toxoplasmotic myocarditis in a case of generalized Fig. 11.16 Toxoplasmotic cyst or pseudocyst in lung section. H &~
toxoplasmosis. The nest of toxoplasms is faintly visible. H&E
PROTOZOAN DISEASES 65

Fig. 11.17 Toxoplasmotic pulmonary lesion. Necrobiosis and acute

inflammation are seen together with a small parasitic cyst. H&E

Fig. 11.20 Toxoplasmotic orchitis with necrobiotic changes at a

seminiferous tubule and interstitial inflammation. H&E

Fig.11.18 Cyst with Toxoplasma gondii organisms in the pleural fluid

of a patient with an acquired. disseminated and fatal toxoplasmosis.
H&E

Fig.11.19 Small toxoplasmotic cyst or pseudocyst in a muscular fibre

or endothelial cell of a small blood vessel in the portal space of the liver
in a case of generalized toxoplasmosis. H&E
Fig.11.21 Higher magnification of Fig. 11.20. A cluster of toxoplasms
may be discerned. H&E
 66 PROTOZOAN DISEASES

Fig. 11.22 Circumscribed necrotic focus in the medulla oblongata in Fig. 11.23 Toxoplasmotic cyst or pseudocyst without inflammatory
a case of neonatal toxoplasmosis reaction in the brain . H&E

Fig. 11.24 Necrobiotic lesions and inflammation in toxoplasmotic Fig. 11.25 Cell nodule in the brain with several toxoplasmotic cysts
encephalitis. H&E or pseudocysts visible in this field. H&E

Fig. 11.26 Toxoplasmotic cysts or pseudocysts in cellular infiltrates Fig.11.27 Toxoplasmotic encephalitis with cell nodule not showing
of the brain with necrobiotic lesions. H&E parasites. H &E
PROTOZOAN DISEASES 67

•
•
•

• ...•
, • • J

....
,
" . "
~

..
•" 0., ' •
.
III
0_
G

... .,
•
Fig.11.28 Perivascular infiltrates in toxoplasmotic encephalitis. Para~ Fig. 11.29 Brain with focal necrobiosis and cell infiltrates. Some
sites are not seen in this field. H &E toxoplasmotic cysts or pseudocysts faintly visible. H&E

.
-. : •
e •

Fig. 11.30 Toxoplasmotic encephalitis with numerous foamy histio~ Fig.11.31 Toxoplasmotic encephalitis. The brownish particles indicate
cytes in this field. Parasites are not seen in this area. H&E antigen-antibody reaction. Immunoperoxidase

Fig.11.32 Higher magnification of features in Fig. 11.31 Fig.11.33 Placenta with several nests of parasites. H&E
68 PROTOZOAN DISEASES

Fig.11.34 Nest of parasites clearly visible in the placental tissue. H&E Fig. 11.35 Toxoplasmotic cyst in the umbilical cord. H&E

. ...; t,
,.

•
.-
Fig.11.36 Toxoplasmotic placentitis. The small granular elements in Fig. 11.37 Higher magnification of Fig. 11.36. The toxoplasms are
the decidua (arrow) were interpreted by experts as Toxoplasma gondii marked with dots. H&E
organisms. H&E

Fig. 11.38 Marked hydrocephalus with cortical atrophy in case of Fig. 11.39 Cut surface of brain with marked oedema. cavities and
neonatal infection with Toxoplasma gondii internal hydrocephalus in case of neonatal toxoplasmosis
PROTOZOAN DISEASES
were not able to detect parasites in the tissue sections of
our cases, although expert parasitologists could
demonstrate the micro-organisms in the same cases (Figs,
11.36 and 11.37).
If the toxplasmotic infection occurs during the second
three months of pregnancy, premature or still birth may
be provoked.
Finally, when infection with T. gondii takes place in
the last stage of pregnancy, pathological disorders in
the pregnancy are almost never seen; birth takes place
normally and the fetus also looks normal. However,
neonatal toxoplasmosis symptoms may manifest them-
selves some weeks or months later in a new-born baby,
who was born apparently normal and healthy. Cerebral
disorders appear, such as fever accompanied by con-
vulsions, states of excitement or lethargy and other signs
typical of encephalitis. The majority of the new-born
babies with toxoplasmosis die in early infancy. In the
autopsies, generalized lesions with parasites are found in
the lungs, myocardium, liver and adrenal glands; these
have provoked interstitial pneumonia, myocarditis, hepa-
titis and the formation of necrotic foci in the adrenals.
The most significant lesions, however, are always found
in the central nervous system. Here, extensive areas of
softening, cyst-like lesions and often pronounced internal
hydrocephalus are seen. These types of lesions had
already been described by Virchow in the last century
and were called 'brains resembling Swiss cheese'. Their
aetiology, obviously, was unknown at that time (Figs.
11.38 and 11.39).
Under the microscope, areas of softening in different
stages of evolution, cellular infiltrates of variable exten-
sions, glial nodules, calcification, vasculitis and throm-
botic processes can be found in the brain. Generally,
parasites are scarce in this type of lesion. It has not yet
been elucidated whethertoxoplasmotic chorioretinitis has
its origin in this sort of congenital infection or of some
other. The percentage of infants with congenital. con natal
or neonatal toxoplasmosis who survive is unknown. Also,
it would be of interest to know what proportion of all
cases of blindness, hydrocephalus, microcephalus, feeble-
mindedness, imbecility and other cerebral damage is
caused by toxoplasmotic infection.
References
1. Enzensberger, W, Helm, E. B., Fischer, P. A. and Stille, W (1985).
Toxoplasmosis of the CNS: an important neurological complication
of AI DS. Trop. Med. Parasit. (Suppl. 11), 36, 19
2. Seitz, H. M. and Kersting, G. (1985). Toxoplasma infection in AI DS
patients. Trop. Med. Parasit. (Suppl. II), 36, 15
12. BABESIOSIS
Introduction
Only isolated cases have been reported in Europe since
1957', but. today, human infections of this protozoan
disease, which is transmitted by ticks, are increasingly
observed and can no longer be considered rare. Cases
have been found in Yugoslavia, France, USSR, Ireland,
USA and Mexic0 2- 5 , but. to our knowledge, this protozoan
infection has, so far, not been found in Venezuela.
Natural Babesia infections are well known in cattle
and rodents. In the former, Babesia bovis and Babesia
divergens are noted and produce the so-called 'bovine
malaria' or piroplasmosis6-8 in tropical countries. Theileria
species are similar to Babesia spp. and may cause the
same disease. In rodents, Babesia microti leads to a latent
localized infection.
There are two clinical forms in man:
69
3. Tschirhart, D. and Klatt. E. C. (1988). Disseminated toxoplasmosis
in the acquired immunodeficiency syndrome. Arch. Pathal. Lab.
Med., 112, 1237
4. Grossniklaus, H. E. et al. (1990). Toxoplasma gondii retinochoroid-
itis and optic neuritis in acquired deficiency syndrome. Report of a
case. Ophthalmology, 97, 1342
5. Matturri, L. et al. (1990). Cardiac toxoplasmos'ls in pathology of
acquired immunodeficiency syndrome. Panminerva Med.. 32, 194
6. Salfelder, K.. Sauerteig, E. and Novoa, M. D. (1987). Pratozoan
Infections in Man. Schwer-Verlag
7. Frenkel. J. K.. Dubey. J. P. and Miller, N. L. (1970). Toxoplasma
gondii in cats. Fecal stages identified as coccidian oocysts. Science,
167, 893
8. Ruiz, A. and Frenkel, J. K. (1980). Toxoplasma gondii in Costa
Rican cats. Am. J. Trop. Med. Hyg., 29, 1150
9. Dubey, J. P. and Gendron- Fitzpatrick, A. P. (1988). Fatal toxo-
plasmosis and enteroepithelial stages of Toxoplasma gondii in a
Pallas cat (Felis manul). J. Protozoal., 35, 528
10. Dubey, J. P. et al. (1990). Acute primary toxoplasmic hepatititis in
an adult cat shedding Toxoplasma gondii oocysts. J. Am. Vet. Med.
Assoc.. 197, 1616
11. Siim, J. C.. Biering-Sorensen, U. and Moller, T. (1963). Toxo-
plasmosis in domestic animals. Adv. Vet. Sci.. 8, 335
12. Dubey, J. P., Ott-Joslin, J., Torgerson, R. W, Topper, M. J. and
Sundberg, J. P. (1988). Toxoplasmosis in black-faced kangaroos
(Macropus fuliginosus melanops). Vet. Parasitol.. 30, 97
13. Cummings, J. F., de Lahunta, A.. Suter, M. M. and Jacobson. R. H.
(1988). Canine protozoan polyradiculoneuritis. Acta Neuropathol.
Berl.. 76. 46
14. Bjerkas.1. and Presthus. J. (1989). The neuropathology in toxoplas-
mosis-like infection caused by a newly recognized cyst forming
sporozoon in dogs. APMIS, 97, 459 .
15. Dubey, J. P. (1988). Lesions in transplacentally induced toxo-
plasmosis in goats. Am. J. Vet. Res.. 49. 905
16. Dubey. J. P. (1989). Lesions in goats fed Toxoplasma gondii
oocysts. Vet. Parasitol.. 15, 133
17. Piekarski, G. (1989). Medical Parasitology. Springer-Verlag
18. Werner. H .. Schmidtke. L. and Thomaschek. C. (1963). Toxoplasma
Infektion und Schwangerschaft. Klin. Wschr.. 41. 96
19. Desmonts. G. and Gonvreur, J. (1974). Congenital toxoplasmosis.
A prospective study of 378 pregnancies. N. Engl. J. Med.. 290,
1110
20. Hay, J .. Graham, D. I. and Aitken, P. P. (1984). Congenital
toxoplasmosis and mental subnormity. J. R. Soc. Med.. 77, 344
21. Dubey. J. P. et al. (1990). Lesions in fetal pigs with transplacentally-
induced toxoplasmosis. Vet. Pathal.. 27. 411
22. Zimmermann, L. E. (1961). Ocular pathology of toxoplasmosis.
Survey Ophthalmol.. 6, 832
23. Piringer-Kuchinka. A. (1952). Eigenartige mikroskopische Befunde
an excidierten Lymphknoten. Verh. Dtsch. Ges. Path .. 36, 352
24. Von Arx, D. P. (1988). Cervicofacial toxoplasmosis. Br. J. Oral.
Maxillafac. Surg.. 26, 70
25. Soto Urribarri, R. and Soto. Taraz6n. S. de (1990). Tratamiento y
evoluci6n de la toxoplasmosis ganglionar. Kasmera. 18. 1
1. The first is mostly observed in Europe, generally takes
a fatal course and is produced by Babesia bovis
or Babesia divergens. It has been seen mostly in
splenectomized patients.
2. The second form is found, predominantly, in the USA.
mostly shows a latent form and is due to Babesia
microti; the patients often have an intact spleen. Latent
Babesia infection can lead to a severe, sometimes fatal.
disease in the recipients of blood transfusions.
Clinical diagnosis is made by microscopic demonstration
of the parasite in Giemsa-stained thin or thick blood films.
Also intraperitoneal inoculation of hamsters with the
blood of patients allows serological diagnosis of the
disease to be made.
 70
Table 4 Developmental cycle of Babesia microti (in part from
Mehlhorn and Schein, 1984)
Intestinal
Camogony
Intestinal epithelium
7
1. Sporozoite from tick saliva (Ixodes species)
2. Multiplication in erythrocyte by binary schizogony resulting
in the formation of merozoites (also in lymphocytes?)
3. Erythrocyte containing characteristic Maltese cross stage
4a. Merozoite; disintegrating merozoite in tick intestine (5a)
5b-8. Gamogony with the formation of 'radiating' bodies (6) in the
intestinal epithelium of the tick
9. A kinete develops from the zygote
10-12. Asexual multiplication of the kinetes in the tick; numerous
sporozoites develop in the salivary gland
The parasite
Species of the genus Babesia belong to the Piroplasmia,
a subclass of Sporozoa. Three are pathogenic for man:
Babesia bovis, Babesia divergens and Babesia microti.
The parasite reservoir hosts are small mammals, e.g.
Microtus species.
Babesia spp. can easily be confused with the malaria
parasite, Plasmodium falciparum. There are quite a few
morphological similarities, but Babesia trophozoites in
erythrocytes are more or less pear-shaped. On the other
hand, they may also be ring-shaped, about 1 pm in
diameter, as are the malaria trophozoites. After division,
Babesia parasites present themselves inside erythrocytes
in pairs or tetrades (also called 'Maltese cross') located
marginally (B. divergens) or centrally (B. microti) within
the erythrocyte. Since we do not possess human material
we show babesiae in the blood of cattle (Fig. 12.1).
The developmental cycle of Babesia microti is seen in
Table 4
PROTOZOAN DISEASES
Pathogenesis
Vectors of these parasites are hard ticks, for example
species of the genus Ixodidae, e.g. Ixodes ricinus or
Dermacentor reticulatus. They ingest the intra-erythro-
cytic stages of Babesia when they feed on blood. Sexual
development takes place in the tick, and later asexual
multiplication and formation of sporozoites in the salivary
glands. When the tick next feeds on blood, the parasites
are transmitted to a new host 9 . Transmission of the
parasites may occur, also, via blood transfusions 10
The symptoms in the infected human host are similar
to those of a recent malaria infection.
Pathology
There are no reports of gross or microscopic tissue lesions
due to Babesia infections. Parasites of this sort can be
found only in blood.
The Babesia organisms are similar to trophozoites of
Plasmodium falciparum inside erythrocytes, as described
in Section 16 on Malaria. In contrast to the malaria
parasites, however, the Babesia organisms may be located
in lymphocytes too. The following structural features have
to be considered for the differential diagnosis. Babesia
organisms do not have: schizonts, gamontes, the stippling
of erythrocytes or pigment I n addition, malaria occurs in
tropical or subtropical countries, while babesiosis is found
worldwide and infection is acquired in regions where
ticks live. Cases with symptoms of malaria resistant to
therapy may be due to Babesia instead of Plasmodium
infection. Babesia organisms may be confused with
haemolysis- induced Pappen heimer bod ies 11.
References
1. Skrabalo, Z. and Deanovic, Z. (1957). Piroplasmosis in man. Report
of a case. Docum. Med. Geogr. Trop" 9, 11
2. Fitzpatrick, J. E. P.. Kennedy, C. C., McGeown, M. G., Oreopoulos,
D. G., Robertson, J. H. and Goyaunwo, M. A O. (1969). Further
details on third recorded case of babesiosis in man. Br. Med. J.. 2.
770
3. Garnham. P. C. C.. Donnelly. J .. Hoogstrael. H .. Kennedy. C C.
and Walton. C. A (1969). Human babesiosis in Ireland: Further
observations and the medical significance of this infection. Br. Med.
J.. 2. 768
4. Western. K. A, Benson, G. D .. Gleason, N. N. et al (1970).
Babesiosis in a Massachusetts resident. N. Eng!. J. Med., 283, 285
5. Anderson, A. E., Cassady, P. B. and Healy, G. R. (1974). Babesiosis
in man. Am. J. C/in. Path.. 62, 612
6. Babes, V (1888) Sur I'hemoglobinurie bactEnienne du boeuf. C.
R. Acad. Sci. (Paris), 107, 692
7. Enigk, K., Friedhoff, K. and Wirahadiredja, S. (1963). Die Piro-
plasmosen der Wiederkiiuer in Deutschland. D. Tierarzt!. Wschr., 70,
422
8. Mcinnes, E. F. et al (1991). An outbreak of babesiosis in imported
sable antelope (Hippotragus niger). J. S. Afr. Vet. Assoc" 62, 30
9. Walter, G. and Weber. G. (1981). Untersuchungern zur Obertragung
(transstadial, transovarial) von Babesia microti, Stamm 'Hannover'l,
in Ixodes ricinus. Tropenmed. Parasit, 32, 228
10. Marcus, L. C.. Valigorsky, J. M" Fanning, W. L.. Joseph, T. and
Glick, B. (1982). A case report of transfusion induced babesiosis.
J. Am. Med. Assoc.. 284. 465
11. Carr. J. M. et al (1991). Babesiosis. Diagnostic pitfalls. Am. J. C/in.
Patho/" 95, 774
PROTOZOAN DISEASES 71

Fig. 12.1 Intraerythrocytic organisms of Babesia bigemina in thin

blood smear of cattle. Giemsa
72
13. SARCOSPORIDIOSIS
Introduction
This parasitosis is one of the four important coccidian
infections. The others are: toxoplasmosis (Section 11).
the most significant from the clinical point of view;
isosporosis (Section 14), today becoming more and
more important in AIDS patients; and coccidiosis, of
interest in veterinary medicine since the causal agents
produce disease In poultry, rabbits and other lower animal
species 12 Practically, the latter does not cause disease in
man and for this reason. it will be omitted here.
Lately, several species have been renamed, the nomen-
clature of parasites has been modified and details of the
evolutionary cycle have been recognized 34 , thus causing
confUSion for the non- parasitologists.
Sarcosporidiosis occurs worldwide wherever rare or
insufficiently cooked beef or pork is consumed. It is
common in North and Central Europe. In Venezuela, to
our knowledge, infections of this sort have not been
reported in man.
. The infection of domestic animals and birds takes place
via numerous differentiable species 5- 8 (Figs. 13.1 and
13.2). All of these parasites go through an obligatory
change of specific hosts. It is easy to infect rodents in
the laboratory experimentally by giving them raw meat
With cysts of Sarcocystis spp.
CI.inica~lx, !t appears that infection with Sarcocystis
bovlhommls IS mild. In contrast infections with Sarco-
cystis suihominis may produce violent intestinal disorders.
In Thailand, fatal intestinal infections have been reported 9 .
Clinical diagnosis. The colourless and fragile sporo-
cysts are not easy to detect during routine stool examin-
ations for worms. Concentration procedures must be
appl ied. I n biopsies of the small bowel. sarcocysts should
be looked for near the epithelium of the mucosa.
The parasite
Sarcocystis species belong to the group Coccidia which
form with the Plasmodia the class Sporozoa. The species
formerly known as Isospora hominis has now been named
Sarcocystis bovihominis and Sarcocystis suihominis.
The species Sarcocystis lindemanni probably does not
eXist; It shou Id not be considered a species specific for
man. I n a critical review by Beaver et a/. 10, only a few
human cases of this sort could be confirmed. The typical
Miescher's tubules, known for almost 150 years, are
observed frequently in the musculature of domestic animals
and do not elicit an inflammatory reaction. Sarcocystis bovi-
canis, S. suicanis and S. bovifelis are not found in man.
Two Sarcocystis species can develop in man: S. boviho-
minis and S. suihominis. Their cycle of evolution is shown
in Table 5.
Merozoites develop in the lamina propria of the intesti-
nal mucosa into oocysts and sporocysts. Merozoites are
banana-shaped intracellular parasites measuring
10-14Jim in length. Oocysts measure about 20 x 10Jim
containing 4 sporozoites (about 14 x 8 Jim) which later
are released from the oocysts (Figs. 13.3-13.6).
Pathogenesis
About 5-1.0 days after eating parasite-containing raw
meat the first oocysts are excreted with the faeces. After
perforation of the walls of the oocysts, sporocysts are
PROTOZOAN DISEASES
released into the intestinal lumen. Oocysts and sporocysts
are excreted over more than 6 weeks. The merozoites
which derive from sporocysts penetrate into the lamina
propria of the small intestine and cause an eosinophilic
inflammation. This may be concluded from the reports of
cases from Thailand and is inferable from the behaviour
of the related species (S. bovicanis etc.) which infect
only animals. In man, haematogenous dissemination of
the parasites into organs other than the small intestine
with formation of cysts has not been reported.
Pathology
In man, only involvement of the small intestine has been
confirmed, although recently, involvement of skeletal
muscles has also been reported in man 1112 . In the animal
host beside the intestine, lesions have also been found
in liver, kidney and brain with formation of whitish
elongated foci, visible to the naked eye.
The enteritis found in man is present more often in the
ileum than in the jejunum. It is characterized by a marked
diffuse oedema of the submucosa and extensive infiltrates
of eosinophilic granulocytes in mucosa and submucosa 9
Oocysts with four sporozoites may be found in tissues.
When more or fewer sporozoites are found in oocysts,
this is due to cutting.
The cysts of sarcosporidians in lower animals are septate
and show the elongated trophozoites of Sarcocystis spp.
References
1. Dubey, J. P. (1976). A review of Sarcocystis of domestic animals
and of other coccidia of cats and dogs. J. Am. Vet. Med Assoc
169,1061 .,
2. Lipscomb, T. P. et al (1989). Intrahepatic biliary coccidiosis in a
dog. Vet. Pathoi, 26, 343
3. Heydorn, A. O. (1977). Beitriige zum Lebenszyklus der Sarkospor-
Idlen. IX. Entwicklungszyklus von Sarcocystis suihominis n. sp. Berf.
Munch. Tieraerzti Wschr., 90, 218
4. Frenkel. J. K. et al. (1979). Sarcocystinae: Nomina dubia and
available names. Z. Parasitenk.. 58, 115
5. Dubey, J. P. eta/. (1991). Acute sarcocystosis-like disease in a dog.
J. Am. Vet. Med Assoc.. 198. 439
6. Gaibova, G. D. and Radchenko, A. I. (1990). An electron micro-
scopic study of the macro- and microcysts of coccidia in the genus
Sarcosystls from buffalo. Tsit%giia, 31, 801
7. Borrow-Hagi, A. et al. (1989). Sarcocystis in Somali camel. Parasito-
logia, 31, 133
8. Latimer. K. S. et al. (1990). Myocardial sarcocystosis in a grand
eclectus parrot (Eclectus roratus) and a Moluccan cockatoo (Caca-
tua moluccensis). Avian Dis.. 34, 501
9. Bunyaratvey, S., Bunyawongwiroi. P. and Nitiyanant. P. (1982).
Human intestinal sarcosporidiosis: report of six cases. Am. J. Trap.
Med Hyg .. 31. 36
10. Beaver, P. C., Gadgil. R. K. and Morera, P. (1979). Sarcocystis in
man: a review and report of five cases. Am. J. Trap. Med Hyg.. 28.
819
11. Pamphlett. R. and O'Donoghue, P (1990). Sarcocystis infection of
human muscle. Aust. N. Z. J. Med, 20, 705
12. Abdel-Mawla, M. M. (1990). Ultrastructure of the cyst wall of S.
lindemanni with pathological correlations. J. Egypt. Soc. Parasito/..
20, 319
PROTOZOAN DISEASES
Table 5 Developmental cycle of Sarcocystis suihominis (Mehlhorn, 1980)
12
C A
Sporogony
II
B
Gamogony
10
A. Schizogony (asexual reproduction)
Fully developed sporocysts (13) are ingested orally and reach the
gastrointestinal canal; frorn thern sporozoites are released (1), which
multiply asexually in the endothelial cells of the liver, kidneys,
lungs and other internal organs and form merozoites (2-5). This
intracellular reproduction can repeat itself many times (5 --> 2)
2. Schizont } the intestinal lumen
3. Merozoite Stages of development In pigs
4. Cysts in the musculature
5. Merozoites from one cyst after consumption of infected muscle
B. Gamogony (sexual development)
Merozoites (5) develop in the lamina propria\to macrogamontes
14. ISOSPOROSIS
Introduction
Infection with Isospora belli does not generally produce
severe disease except in those patients with AIDS. Iso-
porosis is found mostly in Asia and South America and
also in the Mediterranean countries. It is rarely observed
in regions with a temperate climate 1 . We do not know of
any reports of this disease in Venezuela.
The reservoir hosts of Isospora belli are not well known
at present. Experimentally, the gibbon may be infected
with this parasite.
Frequently, infection with Isospora belli is symptomless,
i.e. more than half of the infected persons are only carriers
of this parasite, Symptoms of enterocolitis may be noted
but severe and lasting damage is unlikely2,3 However,
immunodeficient patients may present severe colitis.
In order to obtain a clinical diagnosis, concentration
techniques of stools must be used. The uninucleate
oocysts may be distinguished from sporocysts of Sarco-
sporidia,
73
Sch izogony q
(7) or microgamontes (6) and finally to macrogametes (8) or
microgametes (9)
C. Sporogony
10 The oocyst develops from the zygote
11. Beginning of sporulation (still within the host cell)
12. Oocysts with two sporocysts: the oocyst wall splits open in
13. Free sporocysts containing four sporozoites (capable of infec-
tion)
The parasite
Isospora belli, today, is considered the sole causal agent
of isosporosis. The species, Isospora hominis, has now
been transferred to the Sarcosporidia, S. bovihominis and
S. suihominis.
Only the oocysts of Isospora belli have been recognized
until now. They are oval shaped, 20 x 30 11m in size and
are pointed at one pole with a 'neck-like' constriction 4 ,
Soon, two sporocysts, each containing four sporozoites,
develop from the oocysts (Figs. 14.1-14,3),
Pathogenesis
Transmission of Isospora belli to man occurs via the
resistant oocysts or sporocysts without an intermediate
host. The sporocysts liberate sporozoites which penetrate
the intestinal mucosa. It is quite possible that Isospora in
man behaves like the Isospora species in the dog and in
 74 PROTOZOAN DISEASES

Fig. 13.1 Sarcosporidian cyst in myocardial fibre of cattle. H&E

Fig. 13.2 Sarcocystis sp. cyst in the oesophageal musculature of
buffalo from Thailand. H&E

Fig.13.3 Oocysts of Sarcocystis sp. in the small intestine of dog. H&E Fig. 13.4 Several oocysts of Sarcocystis sp. in the small intestine of
a patient from Thailand. There was a marked eosinophilic enteritis in
this case. H &E

Fig.13.5 Same case as in Fig. 13.4 with higher magnification. Oocysts Fig. 13.6 Same case as Figs. 13.4 and 13.5. The oocysts with their
contain 4 sporocysts which. however. do not show in every section. sporocysts are marked also with this special staining method. Grocott
H&E
PROTOZOAN DISEASES 75

Fig. 14.1 Oocysts of Isospora belli in faeces at low power. Unstained

fresh smear

Fig.14.2 The evolution starts with formation of 2 sporoblasts inside Fig. 14.3 Oocyst of Isospora belli with two sporoblasts. Unstained
oocysts of Isospora belli. Unstained faecal smear faecal smear
76
the cat. Minute microscopic superficial lesions In the
intestinal mucosa may result 5H
Pathology
The ileum and caecum may be involved in infections with
Isospora belli. Gross lesions and forms of Isospora belli
in tissues have not yet been studied in man.
References
1. Piekarski. G. (1989). Medical Parasitology. Springer-Verlag
2. French . J . M .. Whitby. J . L. and Whitfield. A. G. W. (1964) .
15. CRYPTOSPORIDIOSIS
Table 6 Developmental cycle of Cryptosporidium sp. (according to Current. 1985)
5 IJm
t------;
d
a. Sporozoite-containing oocysts from the faeces; b. excysting sporoz -
oites; c. free sporozoite; d. schizont with 6-8 merozoites; e. new infection
of intestinal cells; f. schizogony, which leads to micro- and macro-
Introduction
Infection by cryptosporidians, a coccidian protozoan
parasite, is a relatively 'new' human disease. The parasite
was first described in mice at the beginning of this
century, and has been reported in man only since 1976.
Because of an increased veterinary interest and also the
increasing importance of Cryptosporidium spp. as an
opportunistic parasite, for instance in AIDS patients l - 3 ,
there have been numerous publications on these parasites
in the medical literature of recent years 4- H
The distribution of this organism is worldwide. There
is a high risk of infection for people in rural areas. The
PROTOZOAN DISEASES
Steatorrhea in man infected with coccidiosis (Isospora belli) . Gastro-
enterology. 47, 642
3. Sanders. A. (1967 ). Human infection with Isospora belli . Am J Clin.
Path. , 47, 347
4. Mehlh orn , H. and Peters, W. (1983). Diagnose der Parasiten des
Menschen, einschlie/3lich der Therapie einheimischer und tropischer
Parasitosen. Gustav Fisher-Verlag
5. Webster, B. H. (1957). Human isosoporiasis. A report of three cases
wit h necropsy findings of one case. Am J Trop. Med. Hyg.. 6, 86
6. Trier, J. S. et al. (1974). Chronic intestina l c occidiosis in man:
Intestinal morphology and response to treatment. Gastroenterology,
66, 923
gam antes (g, h, i) and a zygote (j) with a thick-walled oocyst (k). Thin-
walled oocysts, which cause auto-infection can also be formed (I, m)
infection and symptomatic disease is well known in
Venezuela?
The source of human infections are, in addition to pets,
cattle, pigs, sheep and goats, also guinea pigs, mice, rats,
as well as birds, snakes and fish, all of which may be
carriers of cryptosporidians 8 - 17 Several laboratory animal
species may be used for experimental work 18- 21 .
In man, infection may be silent but the symptomatic
disease shows a picture of gastroenteritis with diarrhoea
and watery stools which may continue for 3-14 days.
The considerable loss of water and cramp-like abdominal
pain may be followed by obstipation . Sometimes, weight
PROTOZOAN DISEASES
lass, vamiting and law fever may be assaciated. After
abaut 3 weeks, the symptams disappear ar the condition
becames chranic. In AIDS patients, the course is more
severe and can lead to death.
Far clinical diagnosis, aacysts of Cryptosporidium sp.
may be found in alcahal-fixed staal smears or in sectians
af cell blacks stained with Giemsa. The small oocysts are
nat easy to detect with this staining technique. We prefer
to. stain the aacysts with the Ziehl-Neelsen method.
The parasite
The parasite has been named Cryptosporidium sp and
belongs to the class af Sporazoa. It gaes thraugh a
complicated cycle of evolution which can nat be follawed
using the light microscope: see Table 6. The thick-walled
oocysts which contain four sporozoites are excreted and
spread the infectian transmitting it to a new hast.
The oocysts we see in smears af watery stoals are
spherical in shape and measure 4-7 or 3-6.um in diameter.
They may remain unstained but. with the Ziehl-Neelsen
method, they stain positive. Definite inner structures in
these oocysts cannot be recognized in routinely examined
material. The small banana-shaped sporozaites measure
from 5-6.um.
Pathogenesis
Infections occur by faecal contamination, i.e. by ingestion
af oacysts with faad, water etc. Transmissian takes place
directly from man, or domestic animal, to man without
an intermediate host; predominantly, the parasites are
passed from domestic animals to man. Incubatian time is
3-12 days, the prepatent periad about 1 week and
excretian of oacysts accurs over 2-3 weeks. The sporaza-
ites coming from the oacysts attach themselves to the
surface af the gastrointestinal mucosa This can be
abserved only with the electron micrascape, and the
damage produced cannat be confirmed with the light
micrascope. The sporozaites do. nat invade tissues.
Pathology
The stamach and the lower parts of jejunum or ileum are
invalved. Apparently, lung and biliary infections may
occur, but anly a few cases of this sort have been
described 22 . Gross lesions of cryptasporidiasis are nat
knawn. The attachment of sparozaites to the surface of
the mucosae and the different evolutianary phases af the
parasite on the surface may be studied ultrastructurally
only. The micravilli of the intestinal epithelium may be
destroyed but penetration af the parasite into tissues does
nat accur.
The aacysts in the gastraintestinal lumen stain easily
with the G iemsa and Ziehl-Neelsen methods (Figs. 15.1-
15.3). They are Grocatt-negative and may thus be differ-
entiated fram small yeasts. They are said to. be PAS-
pasitive In histolagical sections, they are nat always
Ziehl-Neelsen-pasitive (Figs. 15.4-15.6).
16. MALARIA
Introduction
Malaria is called also. paludism, swamp or intermittent
fever. It is still a very impartant and uncantralled disease
because the campaigns of eradicatian have nat led to. the
desired results. It is estimated that still 200 million people
are infected.
Circumscribed epidemic zanes af malaria, situated
between 40° latitude north and 30° latitude south, are
77
References
1. Colebunders, R.. Lusakumuni, K., Nelson, A. M., Gigase, P.,
Lebughe, I.. van Marck, E., Kapita, B., Francis, H .. Salaun, J. J.,
Quinn, T. C et al. (1988). Persistent diarrhoea in Zairian AIDS
patients: an endoscopic and histological study. Gut, 29, 1687
2. Rene, E., Marche, C., Regnier, B., Saimot. A. G., Vilde, J. L., Perrone,
C, Michon, C.. Wolf, M, Chevalier, T .. Vallot. T. et al. (1989)
Intestinal infections in patients with acquired immunodeficiency
syndrome. A prospective study in 132 patients. Dig. Dis. Sci., 34,
773
3. Silverman, J. F. eta!. (1990). Small-intestinal brushing cytology in
the diagnosis of cryptosporidiosis in AI DS. Diagn. Cvtopath., 6, 193
4. Tzipori, S.. Smith, M, Birch, C, Barnes, G. and Bishop, R. (1983).
Criptosporidiosis in hospital patients with gastroenteritis. Am. J.
Trop. Med HVg.. 32, 931
5. Burchard, G. D. and Kern, P. (1985). Kryptosporidiose bei Patienten
mit und ohne AIDS. Mit. Oesterr. Ges. Tropenmed Parasit.. 7, 33
6. Casemore, D. p, Sands. R. L. and Curry, A. (1985). Cryptosporidium
species a 'new' human pathogen. J. Clin. Path 01. , 38, 1321
7. Tirado, de A. L. C., Hidalgo, C. and Morales, O. (1988). Brote
familiar de criptosporldiosis en Venezuela. Conv. An. ASOVAC,
Maracay
8. Harp, J. A., Wannemuehler, M. W., Woodmansee, D. B. and Moon,
H. W. (1988). Susceptibility of germfree or antibiotic treated adult
mice to Cryptosporidium parvum. Infect. Immun .. 56, 2006
9. Gibson, S. V. and Wagner, J. E. (1986). Cryptosporidiosis in guinea
pigs: a retrospective study. J. Am. Vet. Med Assoc.. 1, 1033
10. Rehg, J. E, Gigliotti, F. and Stokes, D. C (1988). Cryptosporidiosis
in ferrets. Lab. Anim. Sci., 38, 155
11. Goodwin, M. A. and Brown, J. (1988). Histologic incidence and
distribution of Cryptosporidium sp. infection in chickens: 68 cases
in 1986. Avian Dis.. 32, 365
12. Wages, D. P. and Ficken, M. D. (1989). Cryptosporidiosis and
turkey viral hepatitis in turkeys. Avian Dis, 33, 191
13. Boch, J., Goebel, E. et al. (1982). Kryptosporidose-I nfektion bei
Haustieren. Ber!. Munch. Tierarztl. Wschr., 95, 361
14. Hatkin. J. M. et al. (1990). Experimental biliary cryptosporidiosis
in broiler chickens. Avian Dis.. 34, 454
15. Mair, T. S. et al. (1990). Concurrent cryptosporidium and corona-
virus infections in an Arabian foal with combined immunodeficiency
syndrome. Vet. Rec.. 126, 127
16. Argenzio, R. A. et a!. (1990). Villous atrophy, crypt hyperplasia,
cellular infiltration, and impaired glucose-Na absorption in enteric
cryptosporidiosis of pigs. Gastroenterologv, 98, 1129
17. Mead, J. R. et a!. (1991). Chronic Cryptosporidium parvum infec-
tions in congenitally immunodeficient SCID and nude mice. J.
Infect. Dis., 163, 1297
18. Kim, C. w., Joel, D., Woodmansee, D. and Luft, B. J. (1988).
Experimental cryptosporidiosis in fetal Iambs. J. Parasitol.. 74,1064
19. Bayer, R. et al. (1990). Immunotherapeutic efficacy of bovine
colostral immunoglobulins from a hyperimmunized cow against
cryptosporidiosis in neonatal mice. Infect. Immun .. 58, 2962
20. Levy. M. G .. Ley, D. H .. Barnes, H. J .. Gerig, T. M. and Corbett, W
T. (1988). Experimental cryptosporidiosis and infectious bursal
disease virus infection of specific-pathogen-free chickens. Avian
Dis.. 32, 803
21. Lindsay, D. S., Hendrix, C. M. and Blagburn, B. L. (1988).
Experimental Cryptosporidium parvum infections in opossums
(Didelphis virginiana). J. Wildl. Dis, 24, 157
22. Travis, W. D. et a!. (1990). Respiratory cryptosporidiosis in a patient
with malignant lymphoma. Report of a case and review of the
literature. Arch. Pathol. Lab. Med., 114, 519
found in Central America, Sauth America, Southern
Europe, Africa, Asia, the Philippines and many islands af
the Pacific Ocean. The endemic zones in the South of
the USA have practically disappeared since Warld War
II. Today, malaria infectians in the USA and Northern
Europe are all 'imported' cases. Imported malaria, actually,
is of great importance because symptamatalogy is often
atypical and the diagnosis may not be made at the time.
Each ane of the faur species af Plasmodium has, in
 78 PROTOZOAN DISEASES

Fig. 15.1 Unstained smear of faecal material with numerous organisms Fig.15.2 Smear of faecal material with acid -fast organisms of Crypto-
of Cryptosporidium sp. Phase-contrast sporidium sp. Ziehl - Neelsen

Fig. 15.3 Numerous acid-fast organisms of Cryptosporidium sp. i n Fig. 15.4 Numerous cryptosporidians in the lumen of the intestine in
smear of faeces at high power. Zieh l-Neelsen case of AIDS (tissue section) . Giemsa

Fig.15.5 Same case as Fig. 15.4 H&E Fig. 15.6 Same case as Figs. 15.4 and 15.5. Cryptosporidians are
partly impregnated with faecal material. Giemsa
PROTOZOAN DISEASES 79

Table 7 Intraerythrocytic structures of species of Plasmodium

P. VIVOX P. fo/ciporum P. m%rioe P.ovo/e

Middle aged trophozoite Young trophozoite Young trophozoite

Young trophozoite
with Schueffner's punctuation with two dots annular form

Trophozoite with Mull Ipie trophozoltes Adult trophozoite. Trophozoite. double Infection
basophilic dots band-shaped

Segmented schizont Presegmented schizont Segmented schizont Schizont. progressive form

Young gametocyte Adult macrogametocyte Young mlcrogametocyte Mature gametocyte

addition to diverse vectors. a different geographic distri-
bution. Malaria is becoming endemic in Venezuela again,
after having been completely eradicated in the fifties
and sixties. In 1991 newspapers called it a 'national
emergency' .
Hundreds of species of vertebrates and non-vertebrates
may be infected by some 50 species of the genus
Plasm'odium. Monkeys may be affected naturally by three
species of Plasmodium (P. knowles;' P. cynomolgi and
P. brazilianum). All of these may, rarely, infect man.
Plasmodium berghei and other Plasmodium species are
used for experimental work in various lower animal
species l - 3
The clinical course, at least in endemic regions, is
relatively benign, possibly as a result of a relative immun-
ity. Fatal outcome is observed practically only in infections
with Plasmodium falciparum, and mainly among tourists.
Almost one million deaths are estimated to occur per year.
The denominations of clinical forms of malaria do not
depend only on the bouts of fever. Infections with P.
vivax and P. ovale are called the 'tertiana type'; with P.
malariae the 'quartana type'; and with P. falciparum
80 PROTOZOAN DISEASES

Table 8 Cycle of Plasmodium in man and vector

ANOPHELES
healthy. sucks infected blood
~
Micro and macrogametocytes
'9
Lumen of stomach - - - - - - - - - - - - - _ - - Micro and '9
macrogametes
Cygocyte 10 days
'9 in the
Epithelial cell of the gastric mucosa - - - - - - - - - - - Ookinete (mobile) vector
'9
Oocyst ><
External layers of the gastric wall- - -- - - - -- - - '9 "'C
Sporoplast ~
'9 ~
Salivary glands - - - - - - -- - - - - - - - - - Sporozoite
~
LL--

Bitten by mosquito which injects sporozoites into

o
z
r- - - - - - - - - - - ---, 0

I I I-
:J
-'
J I 0
>
J I W

I
LL
I 0 30 min
I Primary schizont I w Bite
I Cryptozoites
Cryptozoitic merozoites I
..J
u
>- i
Liver
U
I I LL
0 8 days
II Merozoltes Red blood ~ells in blood
I z Bite

1-+--.
0
t
J (I)
___________ J Trophozoites I I-
«
a:
Merozoites
(I)
:J
Cl
12-15 days
Bite
t
r------ ----, r---
Fever

I I I
INTRAERYTH ROCYTI C
I I I SCHIZONT
J
Secondary schizont
J I
J Metacryptozoites I
I I I
H-
Metacryptozoitic merozoites

(i ) --I rr
I RED BLOODLLGAMETOCYTES~
: Merozoites J RED BLOOD _ _ Merozoites
l ! CELLS CELLS . 11 I (III)

I IRed blood ~ells in blood II J

L _____T:P~~t: ~ _ ~

ANOPHELES
~

'tropical', 'pernicious' or 'malignant' malaria. The parasite

For clinical diagnosis. the plasmodians should be recog-
nized in Giemsa-stained thin or thick blood films. Blood
may be drawn at any time between or during the attacks
of fever. The trophozoites of Plasmodium falciparum are
one fifth the size of the diameter of a red blood cell.
The four species of Plasmodium pathogenic for man (P.
vivax, P. falciparum, P. malariae and P. ovale) belong to
the group Haemosporidia of the class Sporozoa. The
characteristic structures of the diverse species of Plasmo-
PROTOZOAN DISEASES
dium in red blood cells are shown schematically in Table
7. Trophozoites, schizonts and gametocytes are illustrated
in Fig. 16.1. The red dot in the trophozoites represents
the nucleus. The Schuffner dots in Plasmodium vivax-
infected human erythrocytes are important in the identifi-
cation of this malarial species 4
Pathogenesis
Man acquires this disease mostly through the bite of an
infected female Anopheles mosquito, which is haema-
tophagous; the male mosquito does not suck blood.
Exceptionally, malaria may be transmitted by blood trans-
fusion. Infections do occur from mosquitos carried via
airports from the tropics to countries with a temperate
climate 5 . The genus Anopheles comprises more than 400
species; 65 of them are able to transmit human malaria.
M ore than 300 species are considered potential vectors.
The evolutionary cycle of Plasmodium is shown schemat-
ically in man and the vector in Table 8.
The three principal stages of evolution are:
1. Sexual reproduction of parasites in the female
Anopheles mosquito, followed later by asexual devel-
opment and sporozoites invading the salivary glands,
through which humans are infected when bitten.
2. Asexual multiplication in the hepatic cells of the host
(pre-erythrocytic stage) with formation of merozoites
and subsequent invasion of red blood cells as tropho-
zoites.
3. Asexual repeated multiplication in the erythrocytes,
causing the clinical picture of the intermittent fever. The
red blood cells may harbour multiple plasmodians 6
The prepatent period (until the appearance of the parasite
in blood) is 8 days for P. falciparum; the incubation period
(until the first bout of fever) 12-15 days. The parasites
destroy erythrocytes with the formation of iron -free malar-
ia
pigment. also called haemozoin. Symptomatology and
the periodic bouts of fever are classical.
Pathology
The destruction of red blood cells leads to pathological
alterations which may be summarized as: terminal circula-
tory disorders, storage phenomena in the PMS system
and consequences of hypoxaemia. Ultrastructural lesions
will not be discussed here 7- 10 With the light microscope,
it may be possible to detect: thromboses, disseminated
intravascular coagulation, micro-infarcts, necroses, haem-
orrhages and a slight inflammatory reaction.
I n fatal cases, characteristics gross lesions are present
in the liver and spleen; these organs show a diffuse
greyish or black colour, while the other viscera and tissues
show a less pronounced blackish colour. Kidneys, liver
and spleen are slightly enlarged. In the chronic forms of
malaria, the splenomegaly is more notable than in the
acute fatal forms. Petechiae and oedema are observed in
the brain (Figs. 16.3-16.8).
Regarding histological lesions, plasmodians are said to
be seen in sections in red blood cells, situated in capillar-
ies. Personally, we have been able to detect parasitized
erythrocytes only in sections of a placenta (Fig 169)
and bone marrow in a P. falciparum infection. This case
was kindly provided by Dr Francis W. Chandler from the
CDC, Atlanta/Georgia, USA Later, after a prolonged
search, we could also see plasmodians in erythrocytes
situated in cerebral capillaries (Fig. 16.10). However,
these intra-erythrocytic structures, which may be tropho-
zoites or schizonts of Plasmodium, were only faintly
visible. The dark dots in red blood cells represent malaria
pigment.
81
By contrast. malaria pigment is present in numerous
organs (Figs. 16.11 and 16.12). It is called haematin or
haemozoin and is a derivative of haemoglobin but is iron
free and difficult to distinguish from formalin pigment.
No histochemical methods are known by which it can be
recognized as such. The malarial pigment is encountered
as small black dots in erythrocytes and as blackish-brown
irregular granules in circulating and fixed macro phages,
above all in von Kupffer cells of the liver. The pigment is
formed in erythrocytes and tissue cells each time an acute
bout of fever, with destruction of red blood cells, occurs.
In autopsies of individuals from endemic zones who
suffered from acute malaria years ago, malaria pigment
was found in viscera only exceptionally, i.e. the pigment
disappears slowly from tissues. Double refraction of
malarial pigment with polarization, as described in the
literature, could not be detected in our material.
Renal lesions are frequent and typical in infections with
Plasmodium species. Characteristic is blackwater fever
or haemoglobinuric nephrosis, an intravasal haemolysis
which leads to haemoglobinaemia and haemoglobinuria.
In the renal tubules, destroyed red blood cells and haemo-
siderin are found in the haemoglobin casts. The dark
colour of the urine, therefore, is not due to malarial
pigment. The latter is not deposited in the spaces of
Bowman nor in renal tubules. Renal insufficiency, azot-
aemia and uraemia are possible consequences of black-
water fever.
The classical malarial lesions in the brain are annular
haemorrhages and granulomas of Durck. Parasites are
not found in the red blood cells situated in the annular
haemorrhages around necrotic foci. The subcortical
granulomas of Durck consist of proliferated glial cells
and appear only in patients who survive more than 12
days. The blockage of capillaries by P. falciparum-infected
erythrocytes seems to be the principal cause of cerebral
malaria 11-14
The placenta is probably the organ where most parasi-
tized red blood cells and pigment accumulate. Plasmo-
dium falciparum matures in the placenta and, conse-
quently, may cause miscarriages, or there may be
transmission through the placenta, as described in the
USA (congenital malaria) 15.16 In the heart thromboses
of coronary arteries, infarcts and interstitial inflammatory
reactions have been described, but only occasionally.
References
1. Gupta. N, Sehgal. R., Mahajan, R. C, Banerjee, A. K. and Ganguly,
N. K. (1988). Role of immune complexes in cerebral malaria.
Pathology, 20, 373
2. Stevenson, M. M. and Kraal, G. (1989). Histological changes in the
spleen and liver of C57BL/6 and A/J mice during Plasmodium
chabaudi AS infection. Exp. Mol. Pathol., 51, 80
3. Wangoo, A. et al. (1990). Immunosuppression in murine malaria:
suppressor role of macrophages and their products during acute
and chronic Plasmodium berghei infection. APMIS, 98, 407
4. Udagama, P. V., Atkinson, C. T., Peiris, J. S., David, P. H., Mendis,
K. N. and Aikawa, M. (1988). Immunoelectron microscopy of
Schuffner's dots in plasmodium vivax-infected human erythrocytes.
Am. J Pa th 01. , 131, 48
5. Majori, G. et al. (1990). Two imported malaria cases from Switzer-
land. Trap. Med. Parasiro/., 41, 439
6. Prasad. R. N. et al. (1990). Detection of multiple invasion of
erythrocytes by Plasmodium vivax. Trap. Med. Parasiro/., 41, 437
7. Nash, G. B., O'Brien, E., Gordon-Smith, E. C and Dormandy, J. A.
(1989). Abnormalities in the mechanical properties of red blood
cells caused by Plasmodium falciparum. Blood, 1, 855
8. Pongponratn, E., Riganti. M., Harinasuta, T. and Bunnag, D. (1989).
Electron microscopic study of phagocytosis in human spleen in
falciparum malaria. Southeast. Asian J Trap. Med. Public Health,
20,31
9. Aikawa, M. (1988). Morphological changes in erythrocytes induced
by malarial parasites. BioI. Cell., 64, 173
 82 PROTOZOAN DISEASES

b c d

• g

Fig. 16.1 Plasmodians: a-d. Trophozoites of Plasmodium vivax

8. Schizont of Plasmodium vivax
f. g. Gametocytes of Plasmodium falciparum
h. Gametocyte in bone marrow. Giemsa + May-Grunwald

Fig.16.2 Schizont in hepatocyte containing cryptozoites or metacryp- Fig.16.4 Cut surface of spleen in the same case as Fig. 16.3
tozoites. Fortuitous finding at autopsy. H&E

Fig.16.3 Cut surface of liver in case of fatal tropical malaria (infection Fig. 16.5 Cut surface of kidney in the same case as Figs. 16.3 and
with Plasmodium falciparum) 16.4
PROTOZOAN DISEASES 83

Fig. 16.6 Bone marrow in the same case as Figs. 16.3-16.5

Fig.16.9 Placenta with plasmodians and abundant deposits of malaria

pigment. H&E

Fig.16.7 Cut surface of brain with oedema and petechiae in the same
infection as Figs. 16.3-16.6

Fig. 16.8 Brain with annular haemorrhage in the same case as Fig.
16.7. The dark dots are granules of malaria pigment inside erythrocytes.
H&E
Fig.16.10 Malaria pigment in Kupffer cells of the liver. H&E
 84 PROTOZOAN DISEASES

Fig.16.11 Schizonts of Plasmodium falciparum seen faintly in a blood

vessel of brain in addition to granules of malaria pigment. Plasmodians.
as a rule. are not seen in tissue sections. H&E

Fig. 16.12 Glomerulus in case of infection with Plasmodium falci-

parum showing malaria pigment. H&E
PROTOZOAN DISEASES
10. Torii, M., Adams, J. H., Miller, L H. and Aikawa, M. (1989).
Release of merozoite dense granules during erythrocyte invasion by
Plasmodium knowlesi. Infect Immun., 57, 3230
11. Aikawa, M. (1988). Human cerebral malaria. Am. J Trap. Med
Hyg., 39, 3
12. Riganti, M. et a/. (1990). Human cerebral malaria in Thailand: a
clinico-pathological correlation, Immuno!. Lett., 25, 199
13. Boonpucknavig, V, et a/. (1990). An immunofluorescence study of
cerebral malaria. A correlation with histopathology. Arch. Patho!.
Lab. Med, 114, 1028
14. Pongponratn, E. et a/. (1991). Microvascular sequestration of
17. PNEUMOCYSTOSIS
Introduction
This disease is also called Pneumocystis pneumonia or
interstitial plasma cell pneumonia due to Pneumocystis
carinii infection. It is an important and worldwide, mostly
opportunistic, infection manifesting Itself as a consequence
of Immunosuppressive treatment, primaryimmunodefici-
ency in premature newborns and AIDS. Here, often,
disseminated forms and/or tumour-like manifestations
with granulomatous tissue reaction are observed 1- B The
number of individuals who become ill with Pneumocystis
pneumonia is increasing constantly. In Venezuela, a trop-
ical country, infections have been confirmed to0 91D
Spontaneous infections have been found in numerous
animal species: rats, mice, rabbits, dogs, cats, cattle and
sheep. Experimentally, pneumocystosis may be produced
easily by injecting rats for 10-14 days with corticosteroids.
The massive, epidemic and often fatal form of the
disease, due to nosocomial infections in premature new-
borns and undernourished infants 11,12, hardly occu rs any
longer, This was a typical infection, with a high prevalence
and a high mortality rate, in the years after World War
II in Europe. Opportunistic infection in adults, as a
consequence of immunodeficiencies of all sorts, is the
most common form of this disease nowadays13. A latent
asymptomatic, pauci -parasitic and pauci- reactive form
exists in immunocompromised and immunocompetent
persons, above all infants. Connatal 14 and familial forms of
the disease and cases with involvement of extrapulmcinary
sites are all rare. In pneumocystosis, commonly, the
characteristic radiological picture of an interstitial pneu-
mon ia exists. Fever is generally present. The patients
become cyanotic and death occurs due to pulmonary
insufficiency and/or associated bacterial bronchopneu-
monia, The prognosis is bad, at least in untreated
patients.
Clinical diagnosis is made by observing Pneumocystis
carinii organ isms, They are demonstrated, rarely, in smears
of sputum or bronchial secretions, A special cytocentri-
fuge is recommended for processing sputa and fluids from
broncho-alveolar lavage 15 . Examination of BAL sediments
is the method of choice today.
I n the books, the Giemsa method is recommended
to stain the parasites, However, in our experience of
examining routine material, the parasites are found only
when stained by the Grocott or toluidine blue method,
Immunobiological methods for diagnosis exist as indirect
fluorescent staining techniques. Not all are reliable.
The parasite
Pneumocystis carinii is the causal agent of the disease,
It has not been encountered living free in nature, nor has
it been cultured in artificial media. It seems to belong, on
the basis of its appearance, to the Protozoa, The majority
of scientists believe it belongs to the class Sporozoa and
subclass Haplosporidia. Others assume it is probably
85
parasitized erythrocytes in human falciparum malaria: a pathological
study. Am. J Trap. Med Hyg., 44, 168
15. Yamada, M., Steketee, R., Abramowsky, C, Kida, M., Wirima, J.,
Heymann, D., Rabbege, J., Breman, J. and Aikawa, M. (1989),
Plasmodium falciparum associated placental pathology: a light and
electron microscopic and immunohistologic study. Am. J Trap.
Med HVg., 41,161 .
16. McGregor, I. A, Wilson, M. E. and Billewicz. W Z. (1983). Malaria
infection of the placenta in the Gambia, West Africa; its incidence
and relationship to stillbirth, birthweight and placental weight
Trans. R. Soc. Trap. Med Hyg., 77, 232
related to the microsporidia. However, in all the classifica-
tions of Protozoa we know, it is not mentioned and some
people consider it a fungus, This was stressed at the
ISHAM Congress, June 1991, in Montreal, Canada.
Some scientists believe that the species of Pneumo-
cystis carinii in man is different from that which is found
in the rat in spite of both being structurally the same.
The Pneumocystis carinii organisms in sections and
smears are spherical, relatively thick-walled, cyst-like
structures. Also, thin-walled parasites are said to be
found. They measure about 3-8,um in diameter and
sometimes appear to be crescent-shaped or coffee bean-
like when the cysts collapse. However, this happens too
with the large yeast-like fungus cells in tissue sections.
The Grocott and toluidine blue methods are the best
techniques for bringing out these parasites. It must be
emphasized, especially, that P. carinii does not stain with
H&E. With the Giemsa method, the organisms are mostly
difficult to recognize, We have seen them with this
technique but only occasionally, in special cases and after
a prolonged search, With the Giemsa and the Rhodamine
stains, 'intracystic bodies' wh ich measure about 1-2 ,um,
can be demonstrated. There may be up to 8 bodies
(sporozoites?) in each parasite. Some investigators have
observed PAS- positive membranes of the P. carinii organ-
isms (Figs, 17,1-17,3), The cycle of evolution of Pneu-
mocystis carinii in man and lower animals is not well
understood (like its taxonomic position), and there are
too many controversial concepts in this subject to venture
a personal opinion,
Pathogenesis
Apparently, a latent infection occurs in humans, rodents
and some domestic lower animals. The portal of entry of
the parasites is the respiratory tract. Then, suddenly,
the saprophyte-like inactive parasites multiply copiously,
transforming into aggressive organisms, and produce
pulmonary disease, They colonize the inferior airways and
become attached to the surface of the bronchiolar mucosa
and alveoli, obstructing the lumens of the cavities mech-
anically. The parasites reproduce rapidly, covering the
remaining respiratory surface, and the patient practically
suffocates, When, in addition, interstitial cell infiltrates
form, the lung function is still more compromised, Extra-
pulmonary sites used to be involved only exceptionally,
but such localizations are now seen with increasing
frequency,
Pathology
The lungs are always involved in infections with Pneu-
mocystis carinii. Additionally extrapulmonary lesions are
found in lymph nodes, bone marrow, liver (Fig. 17.4) and
spleen 1617 Recently, involvement of the small intestine,
choroid and adrenal glands has been reported in AI DS
patients 18- 20 . Here, the granular and foamy masses are
86 PROTOZOAN DISEASES

Fig. 17.1 Cluster of Pneumocystis carinii organisms in smear of a cut

lung surface in a case of massive pneumocystosis. Folds, 'sickle' and
'hat' forms as well as other deformations of the parasites, known in large
yeast-like cells, are seen. Pneumocystis carinii does not stain with H&E.
Grocott

Fig.17.4 In this human liver the parenchyma is replaced by the typical

granular and foamy eosinophilic masses found inside pulmonary alveoli
in cases of pneumocystosis. H&E

Fig. 17.2 Cystic parasites of Pneumocystis carinii showing internal

corpuscles. This is from a smear of the cut surface of a rat lung. Giemsa

.,

\,e,:t '\I'.

• lit .
fI .,.,t:.
• •
'
•• 1

-. • tt

Fig. 17.3 Smear of the same case as Fig. 17.2 with the same internal
corpuscles. Rhodamine; UV light

Fig. 17.5 Unfixed, resected pulmonary specimen with a tumorous

mass (pneumocystoma) in an AI DS patient. (Case of Dr P. Deicke,
Berlin)
PROTOZOAN DISEASES
the same as those present in the pulmonary alveoli.
Additionally, necrobiotic lesions are found with replace-
ment of the organic structure, together with parasites in
these focal lesions.
Grossly, the pulmonary lesions resemble foci of bacterial
bronchopneumonia. Irregularly delimited areas show
increased consistency. Furthermore, large tumour-like
nodules may be found in lungs and other organs 2.37 (Figs.
17.5 and 17.6).
Histologically, the organisms of P. carinii are found
almost exclusively extracellularly and only inside the
pulmonary alveoli. They cannot be detected in sections
stained routinely with H &E. Often, they are arranged in
clusters and attached to the alveolar or bronchiolar walls
(Figs. 17.7-17.9). With the Giemsa method, it is very
difficult and time-consuming to look for this species of
parasites. Sometimes the internal bodies of the organisms
can be seen with the Giemsa method (Fig. 17.2) or with
Rhodamine stain (Fig. 17.3). The best method for staining
pneumocysts is the Grocott technique, both in smears
and in tissue sections. Stained in this way, they look like
small yeast-like fungus cells, occasionally showing single
internal dots (Fig. 17.9). Collapsed or squeezed protozoan
cells may be seen, showing hat-, sickle- and pot-like
forms. Another good stain for P. carinii organisms is
toluidine blue.
In the lumens of the alveoli, it is possible to see single
pneumocysts detached from the walls, together with
typical inhomogeneous, granular and foamy substances.
These are eosinophilic with H&E and stain faintly with
the PAS method (Figs. 17.10-17.13). With the Grocott
method, these intra-alveolar substances often stain black-
ish and may represent debris of destroyed P. carinii
parasites. This foamy alveolar content is found mostly in
infants who also show an interstitial pneumonia. The latter
is said to be missing in immunocompromised patients.
However, we found it recently in an AIDS patient in
Merida. In this case, additional bronchopneumonic foci
were found, apparently due to an associated bacterial
infection (Figs. 17.14 and 17.15). This type of alveolar
content in cases of pneumocystosis can be distinguished
from ordinary oedema or the lipoproteinaceous content
of alveoli observed in histoplasmosis capsulati and other
infections (see the Atlas of Fungal Pathology in this
series). This was previously considered as typical in so-
called lipoproteinosis. In cases of marked PAS-positivity
of the alveolar content an additional lipoproteinaceous
reaction may be present.
In the interstitium, a cellular infiltrate consisting of
mononuclear elements, lymphocytes and sometimes num-
erous plasma cells is found. These interstitial infiltrates
are present mostly in cases of immunocompetent patients,
while they are said to be absent in immunocompromised
patients, as mentioned above.
Exceptionally, a granulomatous reaction has been noted
in cases of pneumocystosis with formation of granulomas
and giant cells 21 (Figs. 17.16-17 .20). I n the latter, para-
sites may be located. Granulomas of this sort cannot be
distinguished from granulomas due to Mycobacterium
tuberculosis. Granulomatous reaction is reported with
increasing frequency in AIDS cases 247 In the necrotic
masses of the nodular (tumour-like) lesions, calcifications
are often found (Fig. 17.21).
Frequently, in cases of infection with Pneumocystis
carinii, another associated opportunistic infection may be
present e.g. cytomegaly or fungal infections.
87
The organisms of P. carinii must be differentiated from
small yeast-like fungus cells, which are also Grocott-
positive.
References
1. Ognibene, F. P.. Masur, H. et al. (1988). Nonspecific interstitial
pneumonitis without evidence of Pneumocystis carinii in asympto-
matic patients infected with human immunodeficiency virus (HIV).
Ann. Imern. Med., 109, 874
2. Hartz, J. W. et al. (1985). Granulomatous pneumocystosis as a
solitary pulmonary nodule. Arch. Patho!. Lab. Med., 109, 466
3. Barrio, J. et al. (1986) Pneumocystis carinii pneumonia presenting
as cavitating and noncavitating solitary pulmonary nodules in
patients with acquired immunodeficiency syndrome. Am. Rev.
Respir. Dis., 134, 1094
4. Bleiweiss, I. et al. (1988). Granulomatous Pneumocystis carinii
pneumonia in three patients with the acquired immune deficiency
syndrome. Chest 94, 580
5. Pilon, V. A. et al. (1987). Disseminated Pneumocystis carinii
infection in AIDS. N. Eng!. J Med.. 316, 1410
6. Leoung, G. (1989). Pneumocystis carinii pneumonia. AIDS Clinical
Care, 1, 9
7. Baumgarten, R. et al. (1990). Pulmonales 'Pneumozystom' -granulo-
matoes-nekrotisierende Pneumozystose bei einem AIDS-Patienten.
AIFO, 6,297
8. Comite du Consensus de la premiere conference de consensus en
therapeutique anti-infectieuse de langue francaise. La pneumocy-
stose au cours de I'infection par Ie VIH. Rev. Pneumo!. Clin., 46,
141
9. Salfelder, K., Schwarz, J., Sethi. K. K., Gonzalez, R., Liscano, T. R.
de and Carlesso, J. (1965). NeumocislOsis, p. 141. Universidad de
Los Andes, MeridaNenezuela .
10. Salfelder, K.. Liscano, T. R. de, Gonzalez, R. and Carlesso, J. (1967).
Pauciparasitic pneumocystosis. Mykosen, 10, 589
11. Vanek. J. and Jirovec, O. (1952). Parasitaere Pneumonie: 'Interstiti-
elle' Plasmazellenpneumonie der Fruhgeborenen, verursacht durch
Pneumocystis carinii. Zbl. Bakl. I. Abt. Orig.. 158, 120
12. Giese, W. (1953). Pathogenese und Atiologie der interstitiellen
plasmazellularen Sauglingspneumonie. Verh. Dtsch. Ges. Path.,
36, 284
13. Gryzan, S.. Paradis, I. L. et al. (1988). Unexpectedly high incidence
of Pneumocystis carinii infection after lung-heart transplantation.
Implications for lung defense and allograft survival. Am. Rev. Respir.
Dis, 137, 1268
14. Pavlica, F. (1966). The first observation of congenital pneumocystis
pneumonia in a fully developed still-born child. Ann. Paediatr., 198,
177
15. Gill, V. J. Nelson, N. A, Stock. F. and Evans, G. (1988). Optimal
use of the cytocentrifuge for recovery and diagnosis of Pneumocystis
carinii in bronchoalveolar lavage and sputum specimens. J Clin.
Microbio/., 26, 1641
16. Jarnum, S.. Rasmussen, E. F.. Ohlsen. A S. and Sorensen, A W.
S (1968). Generalized pneumocystis carinii infection with severe
idiopathic hypoproteinemia. Ann. Int. Med., 68, 138
17. Barnett. R. N., Hull, J. G .. Vortel, V., Kralove, H. and Schwarz, J:
(1969). Pneumocystis carinii in lymph nodes and spleen. Arch.
Path .. 88, 175
18. Carter, T. R., Cooper, P H, Petri, W. A Jr.. Kim,C. K.. Walzer, P.
D. and Guerrant, R. L. (1988). Pneumocystis carinii infection of
the small intestine in a patient with acquired immune deficiency
syndrome. Am. J Clin. Patho!., 89, 679
19. Freeman, W. R, Gross, J. G., Labelle. J .. Oteken, K.. Katz, B. and
Wiley, C. A (1989). Pneumocystis carinii choroidopathy. A new
clinical entity. Arch. Ophthalmo!., 107, 863
20. Unger, P. 0 .. Rosenblum, M. and Krown. S. E. (1988). Disseminated
Pneumocystis carinii infection in a patient with acquired immuno-
deficiency syndrome. Hum. Patho!., 19, 113
21. Schmid, O. (1964). Studien zur Pneumocystis-Erkrankung des
Menschen. I. Mitt. Das wechselnde Erscheinungsbild der Pneumo-
cystis Pneumonie beim Saugling. Konkordante und diskordante
Form. Pneumocystis granulomatosa. Frankf Z. Path., 74. 121
88 PROTOZOAN DISEASES

Fig. 17.8 Cluster of pneumocysts inside pulmonary alveoli in man.

Grocott.

Fig.17.6 Tumour-like focus of pneumocystosis in lymph node. H&E

Fig.17.9 Small cluster of organisms of Pneumocystis carimi attached

to an alveolar wall in a case of pauciparasitic and paucireactive
pneumocystosis in an infant from Merida, observed many years ago.
These organisms were first considered to be yeast-like fungus cells.
Grocott

Fig. 17.10 The typical alveolar content in a human case of massive

pneumocystosis. It is constituted, apparently, by necrotic parasites mixed
with exudate. H&E
Fig. 17.7 Organisms of Pneumocystis carinii in lung tissue with
deformation of parasites. A case of AI DS from Merida. Grocott
PROTOZOAN DISEASES 89

Fig. 17.11 The typical foamy alveolar content of pneumocystosis at

higher power. H&E

Fig.17.14 Interstitial pneumonia with plasma cells in the AIDS case

from Merida. H&E

Fig.17.12 The foamy structure of the alveolar content is clearly seen.

Numerous unstained cyst-like forms may be discerned. Material from
an AIDS patient. PAS

Fig.17.13 The typical foamy alveolar content at higher magnification.

An AIDS case from Merida. PAS

Fig.17 .15 Intra-alveolar exudate with granulocytes in the AIDS case

from Merida . H&E
 90 PROTOZOAN DISEASES

Fig.17.16 Granulomatous reaction. i.e. epithelioid cells in a palisade- Fig. 17.17 The same pattern as in the case of Fig. 17.16. Trichrome
like fashion in the periphery of a pneumocystoma (AIDS patient). H&E (Goldner)

Fig.17.18 Giant cell in the case of Figs. 17.16 and 17.17. H&E Fig.17.19 Pulmonary granuloma in case of infection with Pneuma-
cystis carinii. H& E

Fig.17.20 Anothercase of pulmonary granuloma in a case of pneumo- Fig. 17.21 Pulmonary pneumocystosis with granulomatous reaction
cystosis. Organisms of Pneumocystis carinii may be found inside giant and calcifications. H&E
cells but are not seen in this field. H &E
PROTOZOAN DISEASES
18. BALANTIDIASIS
Introduction
This disease is also called balantidial dysentery or balan-
tidial colitis. It is relatively rare in man because he is
not the principal. but only the secondary or occasional
host. The disease occurs worldwide, mostly in people
dealing with pigs, such as pig breeders, veterinarians and
butchers.
This infection is mostly observed in Eastern Europe, the
former USSR, Asia and the Americas l - 3 . It is well known
in Venezuela where its frequency has not increased over
the last few years4.5. Fatal cases no longer exist (as they
did some 30 years ago). There have been no reports on
this protozoan infection in the medical literature for the
past two years.
Almost all pigs are infected, but they rarely develop
any disease. In addition, monkeys constitute a parasite
reservoir, but. by contrast with pigs, they are sometimes
severely ill. Cats, rabbits, rats and guinea pigs may be
used for experimental i nfection 6 .
I n man, asymptomatic carriers are more common than
cases of disease. Balantidiasis does not have characteristic
symptoms, often takes a chronic course and may remain
undiagnosed. Bloody stools and numerous leukocytes in
faeces are typical of this infection. A fatal outcome may
occur in cases with symptomatology for years, in cases
with perforated ulcers and peritonitis and in cases not
treated adequately7.
Clinical diagnosis is made by examining fresh faeces.
The trophozoites of Balantidium coli are easily recognized
by their size and typical movement. Their cilia are not
seen in permanent preparations and tissue sections. For
diagnostic purposes, balantidians may also be cultured in
artificial media, similar to amoebae.
The parasite
Balantidium coli is the largest protozoan pathogenic to
man. It is ciliated and belongs to the class Ciliophora.
Reproduction takes place asexually by transverse division.
The parasite shows two forms:
1. The trophozoites (or vegetative forms) of Balantidium
coli are spherical or oval shaped. Their maximum size
is 70-150 Jim. Cilia cover the entire surface of the
trophozoites and make them mobile (Figs. 18.1 and
18.2).
2. The cysts are more roundish and a little bit smaller.
The membrane is thicker than that of the trophozoites
and there are no cilia. They do not develop in man.
At one pole of the balantidia, there is a funnel-shaped
invagination (mouth) and, at the other pole, an anal
orifice which is difficult to detect. Bacteria and other
faecal material are the food for the balantidia. Typically,
there are two nuclei, a kidney-shaped macronucleus and
a smaller spherical micronucleus. Vacuoles are present in
the cytoplasm. Balantidium coli may be cultured and
grows like amoeba.
Pathogenesis
Balantidium coli is mostly an inoffensive commensal in
the lumen of the large bowel of pigs. Seldom does the
91
pig become ill. In nature, cysts derive from trophozoites
of B. coli in faeces of pigs. They hardly ever form in man.
Therefore, infection from man to man is rare. The resistant
cysts are ingested with contaminated food or water and
reach the large bowel of man. There they remain in the
intestinal lumen; asymptomatic infection is more frequent
than disease, as in pigs. In certain circumstances, how-
ever, the balantidia become virulent and aggressive and
invade the intestinal wall. causing colitis. Balantidial
dysentery is similar to amoebic dysentery in many respects.
Theories about the action of balantidia, i.e. how and
why the parasites penetrate the intestinal wall. perhaps
by production of proteolytic enzymes, and the following
action of pathogenic bacteria, are still theories and need
confirmation. Haematogenous and lymphogenous dis-
semination of parasites to extraintestinal sites occurs very
rarely.
Pathology
The organ involved is almost exclusively the large bowel
in its entire length (Fig. 18.3). Occasionally, the appendix
is affected 4 and, exceptionally, the terminal ileum. Extrain-
testinal organs are involved very seldom: in single cases,
involvement of mesenteric lymph nodes (Fig. 18.4), liver5 ,
lungs, ureter and bladder, vaginaS and exocervix (Fig.
18.5) has been reported.
Grossly, intestinal lesions are very similar to those
caused by amoebae. Also, ulcers of the mucosa with
undermined borders may be found in the large bowel.
Microscopically, the balantidia in smears and tissue
sections cannot be overlooked because they are so large
and show characteristic structures. I n fresh preparations,
they are very mobile. With routine staining methods, like
H&E (Figs. 18.6 and 18.7), iron haematoxylin and also
the PAS method (Fig. 18.8), they come out well. Special
staining techniques are not necessary for the detection of
these large protozoans. Small balantidia may be confused
with amoebae.
The tissue reaction consists of non-specific inflam-
mation with exudation of leukocytes and abscess for-
mation. Almost always, bacterial infection is associated.
References
1. De Carneri, I. (1958). The frequency of balantidiasis in Milan pigs.
Trans. R. Soc. Trap. Med. Hyg.. 52. 475
2. Arean. V. M. and Koppisch. E. (1956). Balantidiasis. A review and
report of cases. Am. J. Path., 32. 1089
3. Walter, P. D., Judson, F. N .. Murphy, K. D. et al. (1973). Balantidiasis
outbreaks in Truk. Am. J. Trap. Med. Hyg.. 22. 33
4. Jaffe, R. and Kann, C. (1943). Sobre el Balantidium coli en el
apendice y la apendicitis balantidiana. Rev. Sudam. Morfol.. 1, 74
5. Wenger. F. (1943). Absceso hepatico producido por el Balantidium
coli. Kasmera (Univ. Zulia), 2. 433
6. Westphal. A. (1957). Experimentelie Infektionen des Meerschwein-
chens mit Balantidium coli. Z. Trapenmed. Parasit., 8. 288
7. Garcia-Pont. P. H. and Ramirez, .de Arellano, G. (1966). Fatal
balantidial colitis. Bal. Assoc. Med. Puerto Rico, 58, 195
8. Isasa Mejia. G. (1955). Balantidiasis vaginal. Antioquia Med.. 5, 488
 92 PROTOZOAN DISEASES

Fig. 18.1 Trophozoite of Balantidium coli in a faecal smear. H&E

Fig.18.4 Numerous balantidia inside a lymph vessel near a mesenteric

lymph node and several parasites in a lymph vessel of the mesocolon.
H&E

Fig.18.2 Cysts of Balantidium coli in a faecal smear. H&E

Fig.18.3 Perforated ulcers in the ileum and colon due to balantidiasis.

Autopsy material

Fig. 18.5 Marked necrotizing inflammation at the exocervix with

several balantidia. H&E
PROTOZOAN DISEASES 93

Fig.18.6 Numerous balantidia in the wall of the large bowel (balan-

tidial colitis) at low power. H&E

Fig.18.7 Necrotizing colitis with groups of balantidia in the mucosa. Fig.18.8 Balantidia with red granulae in tissue section. PAS
H&E
94
19. MICROSPORIDIOSIS
Introduction
This protozoan disease is also named microsporidosis or
nosematosis. and. lately. other names have been proposed
since other microsporidians have been described. M icro-
sporidiosis. to our knowledge. is not mentioned in Euro-
pean medial literature. The first case of human infection
was reported in 1959 1.
Only a few cases of infection in humans have been
reported. but in recent years. their number has increased.
although named differently. A few cases seem to have
been opportunistic infections. The majority of cases have
occurred in Asia and in children. This disease has not
been reported in Venezuela.
The first natural infection in a lower animal species was
described by Pasteur in 1870 in the silk worm (Bombyx
mori). Later. microsporidians were found in numerous
animal species (dogs. insects. fish and laboratory ani-
mals 2-7). Vervet monkeys and rabbits may be infected
experimentally2.8.
Little is known about the clinical course or form. Only
a few of the human cases have survived. Infections
are known in immunocompromised persons and AIDS
patients. with increasing frequency lately6-17.
Clinical diagnosis is based on the observation of micro-
sporidians in tissue sections of biopsies or in smears of
fluids. Inoculation of laboratory animals cannot be used
as a diagnostic tool because natural infection with micro-
sporidians in these animals is normal.
The parasite
Microsporidia belong to the class Cnidosporidia and
phylum Microspora. The species of the genera Nosema.
Encephalitozoon. Enterocytozoon and Thelohania are the
agents which produce the infection in mammals and.
occasionally. man. The spores of Nosema connori are
oval in shape and measure 2-4 p.m. They stain weakly
with H&E. are sometimes birefractive with polarized light 18
and their membranes stain weakly with the Grocott
method. A characteristic element of the spores is a PAS-
positive corpuscle. With a phase contrast microscope or
an electron microscope. typical filaments arranged in a
spiral form may be discerned.
Pathogenesis
Very little is known about transmission or infection. The
portal of entry seems to be the digestive tract. The cycle
of evolution of the microsporidians is not completely
known at present.
Pathology
Mostly. musculature (Fig. 19.1) is involved. although
several other tissues may be affected too. In some reported
cases17.19.20. the ocular cornea was invaded by this para-
site. and. in another21. tumour cells of a pancreatic
carcinoma harboured microsporidians. Intestinal involve-
ment has been reported mostly in AIDS patients 12- 15 .
Details of gross lesions are not known.
Microscopically. the spores of microsporidians are
arranged in clusters. mostly intracellularly. Some micro-
PROTOZOAN DISEASES
sporidians show a halo (Fig. 19.2). others a PAS-positive
dot (Fig. 19.3) and others are slightly Gram-positive. The
Grocott-positive membranes indicate fungal cells (Fig.
19.4).
Regarding differential diagnosis of the microsporidians.
all small micro-organisms and inclusion bodies must be
mentioned (Figs. 19.5 and 19.6). Muscle fibres may be
invaded by the following protozoa: Trypanosoma cruzi.
Toxoplasma gondii. Sarcocystis sp. and Nosema connori.
References
1. Matsubayashi. H. et al. (1959). A case of Encephalitozoon-like
body infection in man. Pathology. 67. 181
2. van Dellen. A. F.. Stewart. C. G. and Botha. W. S. (1989).
Studies of encephalitozoonosis in vervet monkeys (Cercopithecus
pygerythrus) orally inoculated with spores of Encephalitozoon
cuniculi isolated from dogs (Canis familiaris). Onderstepoort. J. Vet.
Res.. 56. 1
3. Van Heerden. J .. Bainbridge. N.. Burroughs. R. E. and Kriek. N. P.
(1989). Distemper-like disease and encephalitozoonosis in wild
dogs (Lycaon pictus). J. Wildl. Dis.. 25. 70
4. Cutlip. R. C. and Beall. C. W. (1989). Encephalitozoonosis in arctic
lemmings. Lab. Anim. Sci.. 39. 331
5. Ansbacher. L.. Nichols. M. F. and Hahn. A. W. (1988). The influence
of Encephalitozoon cuniculi on neural tissue responses to implanted
biomaterials in the rabbit. Lab. Anim. Sci. 38. 689
6. Powell. S. et al. (1989). Microsporidiosis in a lovebird. J. Vet.
Diagn. Invest.. 1. 69
7. Bjerkas. I. (1990). Brain and spinal cord lesions in encephalito-
zoonosis in mink. Acta Vet. Scand.. 31. 423
8. Wicher. V. et al. (1991). Enteric infection with an obligate intracellu-
lar parasite, Encephalitozoon cuniculi. in an experimental model.
Infect. Immun .. 59, 2225
9. Margileth, A. M .. Strano, A. J .. Chandra. R. et al. (1973). Dissemi-
nated nosematosis in an immunologically compromised infant. Arch.
Path .• 95. 145
10. Zender, H. 0 .. Arrigoni. E.. Eckert. J. and Kapanci. Y. (1989). A
case of Encephalitozoon cuniculi peritonitis in a patient with AIDS.
Am. J. Clin. Pathol.. 92. 352
11. Rijpstra, A. C.. Canning. E. U. et al. (1988). Use of light microscopy
to diagnose small-intestinal microsporidiosis in patients with AIDS.
J. Infect. Dis., 157, 827
12. Greenson, J. K. et al. (1991). AIDS enteropathy: occult enteric
infections and duodenal mucosal alterations in chronic diarrhea.
Ann. Intern. Med., 114, 366
13. Orenstein, J. M. et al. (1990). Intestinal microsporidiosis as a cause
of diarrhea in human immunodeficiency virus-infected patients: a
report of 20 cases. Hum. Pathol.. 21, 475
14. Kotler, D. P. et al. (1990). Small intestinal injury and parasitic
diseases in AIDS. Ann. Intern. Med., 113, 444
15. Peacock, C. S. et al. (1991). Histological diagnosis of intestinal
microsporidiosis in patients with AIDS. J. Clin. Pathol., 44, 558
16. Shadduk, J. A. et al. (1990). Isolation of a microsporidian from a
human patient. J. Infect. Dis.. 162, 773
17. Friedberg, D. N. et al. (1990). Microsporidial keratoconjunctivitis
in acquired immunodeficiency syndrome. Arch. Ophthalmol.. 108,
504
18. Tiner, J. D. (1988). Birefringent spores differentiate Encephalito-
zoon and other microsporidia from coccidia. Vet. Pathol., 25, 227
19. Ashton, N. and Wiransnha, P. A. (1973). Encephalitozoonosis
(nosematosis) of the cornea. Br. J. Ophthalmol.. 57, 669
20. Davis, R. M. et al. (1990). Corneal microsporidiosis. A case report
including ultrastructural observations. Ophthalmology, 97, 953
21. Marcus, P. P., Van der Walt, J. J. and Burger, P. J. (1973). Human
tumour microsporidiosis. Arch. Path., 95, 341
PROTOZOAN DISEASES 95

Fig.19.1 Cluster of microsporidians in a muscle fibre of the diaphragm. Fig. 19.2 Spores with a halo in a lesion caused by microsporidians.
with inflammation in the vicinity. H&E H&E

Fig.19.3 Spores with PAS-positive dots inside a muscle fibre. PAS Fig. 19.4 These microsporidians at high power are partly Grocott-
positive. Groeott

Fig.19.5 Cytoplasmic inclusion bodies in carcinoma cells (metastasis Fig. 19.6 Same case as Fig. 19.5. The inclusion bodies. variable in
of gastric carcinoma) are similar to microsporidians. PAS size, are positive with this special staining method, Grocott
 Helminthic diseases III

The parasitic helminths belong to multicellular living
organisms (Metazoa of the fifth kingdom). are male.
female or hermaphrodite and do not usually multiply in
man. They may live in the human digestive tract or in
determined tissues. and they may produce up to 100000
eggs per day. Many species have teeth or hooks for
adherence to the wall of hollow organs.
Sources of infection and portals of entry are listed in
Table 9.
Frequently. the presence of worms in an individual is
not noticed. Signs of worm infection may be:
1. Loss of weight because the worms consume too much
food destined for the host;
2. Anaemia. because worms suck blood from the host;
and
3. Obstruction and/or perforation of hollow organs.
Consequences of their toxic action may be allergies or
inflammation with eosinophilic leukocytes in the blood
and/or in tissues. Often. the number of parasites deter-
mines symptoms and severity of disease. For the prepatent
period and the lifespan of helminths in man. see Table 10.
The diseases produced by the three large groups of
helminths are: A. nematodiasis. B. cestodiasis. and C.
Trematodiasis (flukes).

Table 9 Principal sources of infection in helminthic diseases

Source of infection Species of parasite

Oral infection
1. Drinking water
Ingestion of cyclops and larvae Dracunculus
Sparganum
Salad and vegetables contaminated by human faeces Ascaris. Trichuris
Lettuce. radish. all kinds of fruit Cysticercus cellulosae
Cress Fasciola
Water nuts Fasciolopsis
2. Uncooked food
Meat
Pork Taenia solium. Trichinella spiralis
Cattle Taenia saginata
Fish Diphyllobothrium latum
Several species Opisthorchis
Crabs and crayfish Paragonimus
3. Dirt
Earth Ascaris. Trichuris. Cysticercus cellulosae. Echinococcus
Anus-finger-mouth Enterobius. Hymenolepis nana
Cysticercus cellulosae
House dust Enterobius
Contact with dogs Echinococcus

Percutaneous infection
1. Soil Ancylostoma. Necator Strongyloides
2. Water Schistosoma
Various species causing Cercaria dermatitis
3. Insect bite Species of Filaria

A. NEMATODIASIS
The nematodes. threadworms or roundworms belong to
the phylum of Nemathelminthes; they are non-segmented
parasites and have separate sexes. They measure from a
few mm (Strongyloides stercoralis. almost invisible to the
naked eye) up to 60cm (Dracunculus medinensis) and
all have pointed ends. Tables 11 and 12 show structural
details of the digestive tract. the separate genital organs
and the cuticle on the surface with collagen fibres which
produce contractions. There are several developmental
stages from the egg. through 4 moults of larvae. to the
mature worm. Details of larvae. whether rhabditiform or
filariform. will not be discussed here.
Four different types of cycles of evolution in man may
be distinguished:
1. The Enterobius type
The ova are ingested ~ mature in the intestinal tract
2. The Ascaris type
Ova are ingested ~ larvae in the digestive tract ~
transenteral passage ~ blood ~ heart ~ lungs ~
pharynx ~ digestive tract (maturing)
3. The hookworm type
Ova in nature become larvae ~ transcutaneous pass-

96
HELMINTHIC DISEASES 97

age --+ blood heart --+ lung --+ pharynx --+ digestive
tract (maturing)
4. The Trichinella type
Encysted larvae are ingested with meat --+ larvae are
set free in digestive tract --+ transenteral passage --+
blood --+ heart --+ musculature (larvae become again
encysted)
Recently. strongyloidiasis as an opportunistic infection
has become important because latent infections of this
kind are exacerbated in immunocompromised individuals.

20. ENTEROBIASIS
I ntrod uction
This disease is also named oxyuriasis or pinworm infec-
tion. It occurs worldwide and is perhaps one of the most
frequent worm infections. It is found mainly in regions
with temperate or colder climates and in middle and upper
class people. i.e. contrary to most other worm infections.
it is observed in wealthy individuals. Furthermore. it is
seen predominantly in children. The infection is unusual
in Venezuela. This parasite does occur in lower animals
but only occasionallyl; it develops in man without inter-
mediate hosts.

Table 10 Prepatent period of various helminths (eggs in the faeces or microfilariae in the blood). From Piekarski.
G. (1989) Medical Parasitology

Developmental stage Prepatent period Lifespan in man

(extreme values)

Nematodes
Trichuris trichiura Egg 60-90 days Several years
Enterobius vermicularis Egg 37-101 days ca. 100 days
Ascaris lumbricoides Egg 50-80 days 1-1.5 years
Ancylostoma duodenale Egg 35-42 days 5-12 years
Necator american us Egg 35-42 days 5-8 years
Strongyloides stercoralis Larva 17-28 days 20 years
Trichostrongylus orientalis Egg 25-30 days
Wuchereria bancrofti Blood ca. 1 year 17 years
Brugia malayi Blood 50-60 days 8-10 years
B. timori Blood 90 days
Blood ca. 1 year 17 years
Loa loa
Microfilariae Skin 12-15 months 15-18 years
Onchocerca volvulus
Mansonella ozzardi Blood ?
Dipetalonema perstans Blood 8-12 months
D. streptocerca Skin 3-4 months7

Cestodes up to 20 years
Proglottid 77-84 days
Taenia saginata up to 25 years
Proglottid 35-74 days
Taenia solium 2 weeks to months
Egg 14-28 days
Hymenolepis nana 15-20 years
Egg 18-21 days
Diphyllobothrium latum
Proglottid 20 days
Dipylidium caninum

Trematodes
Fasciolopsis buski Egg ca. 30-90 days 6 months
Echinostoma ilocanum Egg
Metagonimus yokogawai Egg 10-14 days 2 years
Heterophyes heterophyes Egg 7-8 days 2-4 months (?)
Schistosoma mansoni Egg (lateral spine) 49 days up to 30 years
Schistosoma intercalatum Egg (terminal spine) 50-55 days up to 25 years
Schistosoma japonicum Egg Small lateral 20-26 days
Schistosoma mekongi Egg knob 35 days

Table 11 Typical features of nematodes. Enterobius. about 10mm (female. above) and 4mm (male.
below) in length

Oesophagus

Ovary Uterus Oviduct

Spicule

Papillae
Cervical Intestine Testis Vas deferens
alae
98
Table 12 Schematic cross-section from various groups of female nematodes
Anterior
portion
Posterior
portion
Trichocephalus
Enterobius
Dracunculus
The clinical picture is typical. The children become
sleepless, restless and inattentive. The bad feeling, and
sometimes diarrhoea, may mimick appendicitis. In the
genito-anal region, the parasites may lead to marked
scratching with cutaneous irritation. Clinical diagnosis is
made by looking for pinworm eggs in anal swabs or on
strips of clear adhesive tape from the genito-anal region.
Adult worms may be found in smears from stools. Eggs
or worms may be stained with toluene blue.
The parasite
This roundworm is called Enterobius vermicularis or
Oxyuris vermicularis. It measures from 2-13 mm, the
females being larger (Figs. 20.1 and 20.2). Tables 11 and
12 show the structure of male and female pinworms
schematically. These worms may be vectors of micro-
organisms 2.3 . Characteristically, the ova of E. vermicularis
are oval and flattened on one side; they measure 55 x
25 J.Lm (Fig. 20.3).
Pathogenesis
The ova are ingested. Autoinfection may take place,
mainly in children. Larvae and eggs in the anal and genital
region lead to scratching, and reach the mouth via the
fingers. Infections may also occur by direct contact of the
HELMINTHIC DISEASES
Hookworm
Strongyloides Filaria
Lateral
cords
Splrurid Ascaris
hands with clothes, dust or food where worm eggs may
be present. Retrograde migration of larvae from the anal
region to the gut may occur4 , usually in adults. The larvae
reach the appendix; here, male pinworms are seen more
frequently than female 5.
After oral ingestion, larvae enter the small intestine
where they mature. The male worms die soon after mating.
During the night. the females migrate to the anal region
where they lay their eggs. Within a few minutes they can
lay up to 10000 eggs. Adult worms, larvae and eggs do
not penetrate into tissues.
Pathology
The adult worms are found in the terminal small intestine,
the region of the ileocaecal valve, the appendix and the
caecum (Fig. 20.4). The parasites, larvae and eggs may
produce superficial irritation but. as a rule, do not invade
mucosa or skin (Fig. 20.5). They do not cause appendi-
citis 5,6
References
1. Zhang, G. W. et at. (1990). The presence of pinworms (Enterobius
sp.) in the mesenteric lymph nodes, liver and lungs of a chimpanzee,
Pantroglodytes. J. Helmimhol" 64, 29
2. Burows, R. B. and Swerdlow, M. A. (1956). Enterobius vermicularis
HELMINTHIC DISEASES 99

o (

Or..:. ft
o
Fig. 20.2 Fore-end of female Enterobius vermicularis and numerous
eggs of th is nematode

{\ U·
'b
Fig. 20.1 Mature male Enterobius vermicularis (pinworm) Fig.20.3 Eggs of pinworm. almost colourless. ovoid and flattened on
one side. i.e. with characteristic structural features

Fig. 20.4 Pinworms in the lumen of the appendix. H&E Fig. 20.5 Superficial tissue invasion of pinworms into the intestinal
mucosa. H&E
100
as a probable vector of Dientamoeba fragilis. Am. J. Trap. Med. Hyg.,
5, 258
3. Ockert, G. (1972). Zur Epidemiologie von Dientamoeba fragilis. II.
Versuch der Obertragung der Art mit Enterobius-Eiern. J. Hyg.
Epidemiol. Microbiol. Immunobiol., 16. 222
4. Schuffner. W. and Swellengrebel. N. H. (1949). Retrofection in
21. ASCARIASIS
Introduction
This worm infection was described more than 2000 years
ago'. Ascaris lumbricoides is cosmopolitan. It is found
more frequently in children than in adults. It has been
estimated that about a quarter of the world population is
a carrier of this worm 2 . The prevalence of ascariasis is
especially high in tropical countries. In Venezuela, we
find it often in combination with whipworms and hook-
worms in the intestinal tract of members of the rural
population where it occasionally causes severe complica-
tions.
Man is the only host. Ascariasis is not seen in lower
animals. Piglets and pigs may be infected experimentally
with A. suum and A. lumbricoides3-5.
Clinically, this intestinal parasitosis is often asympto-
matic. Symptoms may consist of allergic reactions, abdo-
minal pain, anaemia and numerous other symptoms due
to diverse complications (see Pathology below). Com-
plications may be fatal. The death rate is estimated at 6
per 100000 carriers. Weakness and lowered resistance,
as well as immunological defects, may be due to a massive
deprivation of food and vitamins by the worms.
Clinical diagnosis is made by finding the parasites or
their eggs in stools or vomited masses. Transient pulmon-
ary infiltrates or worms in hollow organs may be detected
by X-ray. Eosinophilia of the blood may indicate worm
infection.
The parasite
Ascaris lumbricoides is called the ascarid roundworm and
is one of the largest and most common intestinal parasites
Table 13 Ascaris lumbricoides. Schematic representation of the life cycle
Oesophagus
_ - - -65 - - - - . ~ if
Ir
days
Trachea
t
Lungs
3 days t
Portal system
(liver. heart)
1 ..
Duodenum.
Egg releases
-4-_ _ _ _ _ _ _ _ _ _ _ _
mature larva
Up to 7 years
HELMINTHIC DISEASES
oxyuriasis. A newly discovered mode of infection with Enterobius
vermicularis. J. Parasit.. 35, 138
5. Williams, D. J. and Dixon, M. F. (1988). Sex, Enterobius vermicularis
and the appendix. Br. J. Surg., 75, 1225
6. Symmers, W. S. C. (1950). Pathology of oxyuriasis. Arch. Path., 50,
475
in man. The mature worms measure up to 40 cm in length
and may survive 1-2 years in the human body. They look
like earthworms, hence their denomination. The female
worms are a little larger than the males. They may lay up
to 240000 eggs per day. Fertilized and non-fertilized
eggs may be distinguished morphologically; they measure
60-70 x 50,um and, typically, are surrounded by three
coverings.
Pathogenesis
The ova excreted in the faeces may remain infectious
for many months or even years in appropriate humid
conditions. They are ingested and go through a special
developmental cycle, called the Ascaris type, which was
mentioned in the introductory remarks about nematodiasis
and is shown schematically in Table 13. There is no
intermediate host.
The larvae go through consecutive moults while passing
through the small bowel wall. They may cause the Loffler
syndrome in the IUllgs, and the so-called larva migrans
condition which will be discussed separately ~Section
37). Migrating Ascaris larvae may carry bacteria.
Pathology
The adults of Ascaris lumbricoides normally inhabit the
small intestine, but may be found in all body cavities, and
leave through all body orifices. Sometimes, they are
present in large numbers in the lumen of the small bowel
Adults in
the intestine
Eggs in faeces
10-15 days
Eggs with infective
larvae in soil
HELMINTHIC DISEASES
and may produce mechanical ileus, volvulus or intestinal
perforation, followed by purulent peritonitis 6 (Figs. 21.1-
21.4). Also, a granulomatous peritonitis may be seen
due to worm eggs 7 (Figs. 21.5-21.7). Occasionally,
perforation of the intestinal wall takes place postmortem.
Coming to, and remaining in, the appendix, they may
cause appendicitis. When the worms invade pancreatic
ducts, acute obstructive pancreatitis may be the conse-
quence. More often, they obstruct bile ducts and provoke
purulent cholangitis and liver abscesses 8- 11 (Figs. 21.8-
21.10). Also, formation of tumour-like nodules or necrotic
foci, sometimes called ascaridiomas, may take place in
the liver. In the abscesses and ascaridiomas (Figs. 21.11
and 21.12), numerous Ascaris eggs may be encountered
(Fig. 21.13). Obstruction of the nasolacrimal duct by this
nematode is exceptional 12 .
The passage of the larvae of A. lumbricoides (and of
other worms) through the lungs leads to focal and
transient eosinophilic infiltrates (Loffler syndrome). In
these organs, the lesions are usually found fortuitously
when the organs are examined histologically at autopsy
since these foci may not be detected with the naked eye.
Microscopic lesions caused by these larvae in other
organs will be described later (Section 37).
References
1. Ferreira, L. A. et al. (1980). The finding of eggs and larvae of
parasitic helminths in archaeological material from Unai. Minas
22. TRICHURIASIS
Introduction
This helminthic disease, also called whipworm infection,
occurs worldwide but is more common in tropical coun-
tries than in temperate zones. Here, 90% of the population
may be carriers and, in Venezuela, whipworms are very
common. Children are affected most often; hundreds of
these worms may be encountered in the intestinal tract.
The whipworms found in dogs and monkeys do not
appear to be identical to those found in man. However,
Trichuris ova may be transmitted, experimentally, from
monkeys to man 1.
Clinically, this intestinal parasitosis is usually of minor
importance, but heavy infections can cause severe dam-
age to man, especially young children, occasionally result-
ing in death2-4. Most infections are asymptomatic,
although numerous parasites may impair the nutrition of
the host. Since trichuriasis frequently occurs together
with uncinariasis and ascariasis, it cannot be determined
which parasites cause the damage. Abdominal pain and
all kinds of intestinal symptoms may be due to infection
with Trichuris trichiura.
For a clinical diagnosis, infection with whipworms may
be detected by examination of the stools where the typical
eggs of T. trichiura can be found. Blood eosinophilia is
present as in other worm infections.
The parasite
Trichocephalus trichiuris is a synonym of Trichuris trich-
iura and, commonly, this worm is named whipworm.
Without the long whip, the mature whipworm measures
3-6 mm. The whip is a thin thread-like anterior part,
previously thought to be a tail (Fig. 22.1). The worm
adheres to the intestinal mucosa with the whip and may
live for more than a year in the intestinal tract of man.
Eggs of T. trichiura have a typical appearance, showing
two polar prominences, and cannot be confused with eggs
of other worms. They measure 50 x 25 J.lm (Fig. 22.2).
101
Gerais, Brazil. Trans. R. Soc. Trap. Med. Hyg.. 74, 798
2. Crompton, D. W. T. (1988). The prevalence of ascariasis. Parasitol.
Today, 4, 162
3. Adedeji, S. O. et al. (1989). Synergistic effect of migrating Ascaris
larvae and Escherichia coli in piglets. J. Helmithol.. 63, 19
4. Bernardo, T. M. et al. (1990). A critical assessment of abattoir
surveillance as a screening test for swine ascariasis. Can. J. Vet.
Res.. 54, 274
5. Bernardo, T. M. et al. (1990). Ascariasis, respiratory diseases and
production indices in selected Prince Edward Island swine herds.
Can. J. Vet. Res., 54, 267
6. Tie-Hsiung, T. and Pin-Liang, C. A. (1963). A case report of
panperitonitis due to perforation of Meckel's diverticulum caused
by ascariasis. J. Formosa Med. Assoc.. 62, 89
7. Walter. N. and Krishnaswami, H. (1989). Granulomatous peritonitis
caused by Ascaris eggs: a report of three cases. J. Trap. Med. Hyg..
92,17
8. Teoh, T. B. (1963). A study of gallstones and included worms in
recurrent pyogenic cholangitis. J. Path. Bact., 86, 123
9. Strauszer. T. and Candido, J. (1965). Ascaridiasis intracoledociana
diagnosticada por colangiografia postoperatoria (communicaci6n
de seis cas os, uno de e'llos fatal). Bol, Chil, Parasit.. 20,7
10. Schmid, K, O. (1965), Intrahepatische cholangio-ascaridiasis, Lan-
genbecks Arch. Klin. Chir.. 310, 64
11. Gayotto, L. C. et al. (1990). Hepatobiliary alterations in massive
biliary ascariasis, Histopathological aspects of an autopsy case, Rev.
Inst. Med. Trop, Sao Paulo, 32, 91
12, Cunha, M. C. et al. (1989). Obstruction of the nasolacrimal duct
by Ascaris lumbricoides. Ophthal. Plast. Reconstr, Surg.. 5, 141
Pathogenesis
The infection and developmental stages are of the Enter-
obius type. The ingestion of eggs into the gut leads
directly to the release of larvae from the eggs which end
up and mature in the large bowel. Complicated cycles of
evolution, migration to other organs and intermediate
hosts do not exist. The prepatent period is about 90 days.
The superficial penetration into Hie intestinal mucosa by
the adult worm is the only damage and leads to a mild
inflammatory reaction,
Pathology
Mature whipworms are found in the caecum, around the
ileocaecal valve and in the large bowel. Since they do
not suck blood - like the hookworms, for instance - they
always appear white or pale and are easy to detect (Fig.
22.3).
The penetration of their slender anterior part into the
intestinal mucosa does not reach the submucosa (Fig.
22.4). Mononuclear cell infiltrates in the stroma of the
mucosa are the consequence of an occasional mucosal
invasion and are minimal.
References
1, Horii. y, and Usui. M, (1985), Experimental transmission of Trichuris
ova from monkeys to man, Trans, R, Soc, Trap, Med. Hyg.. 79, 423
2. Gilman, R. H. et al. (1983). The adverse consequences of heavy
Trichuris infection. Trans. R. Soc, Trap. Med. Hyg.. 77, 432
3, Cooper, E, S, and Bundy. D. A. P. (1988). Trichuris is not trivial.
Parasitol. Today, 4. 301
4, Arenas. J, V .. Brass, K. and Romero Toanyo. H, (1965). Tricocefalosis.
Estudio clinico-patoI6gico. GEN Caracas. 20, 177
102 HELMINTHIC DISEASES

Fig. 21.1 Numerous roundworms (Ascaris /umbricoides) filling up the Fig. 21.2 Numerous roundworms perforating the intestinal wall
small intestine

Fig. 21.3 Intestinal perforation by several roundworms. in close-up Fig. 21.4 Roundworm . cut transversally. in the intestinal submucosa
with massive haemorrhages. H&E
HELMINTHIC DISEASES 103

Fig.21.5 Eggs of Ascaris lumbricoides partly necrotized in the granu- Fig.21.6 Two eggs of Ascaris lumbricoides with foreign body giant
lation tissue of the abdominal wall (after intestinal perforation of worms) . cells in an ascaridioma of the liver. H&E
The ova are not easily recognizable as deriving from this sort of worm.
H&E

Fig.21.7 Close-up of a foreign body reaction. Ascaris eggs surrounded Fig.21.8 Adult roundworm (Ascaris lumbricoides) in a bile duct. H&E
by giant cells. The eggs of Ascaris lumbricoides in tissues are not easily
and surely recognizable as such. H&E

Fig. 21.9 Ascaris egg in the lumen of a bile duct together with Fig. 21.10 Testicle with spermatozoa of the roundworm in Fig. 21.8
leukocytic exudate. H &E at high power. Male bachelors of Ascaris lumbricoides often migrate
into the bile and pancreatic ducts in search of female worms. H&E
104 HELMINTHIC DISEASES

Fig. 21.11 Ascaridioma in the liver at low power. Numerous Ascaris Fig.21.12 Another field of an 'ascaridioma' of the liver with a fibrous
eggs may be seen in the necrotic ('tumour') masses. H &E capsule. Worm eggs are also seen. H&E

Fig.21.13 Ova of Ascaris lumbricoides from hepatic ascaridiomas and

abdominal wall granulomas due to worm eggs. Mostly. they are deformed
and not recognizable as Ascaris eggs. H&E
HELMINTHIC DISEASES 105

Fig. 22.1 Two whipworms (Trichuris trichiura) with the thread -like Fig.22.2 Trichuris trichiura egg with the typical two polar prominences
thin anterior part which mimicks a tail

Fig. 22.3 Numerous whitish whipworms in the caecum. Compare Fig.22.4 Two whipworms in the lumen of the appendix, one contain-
with Fig. 23.6 ing numerous eggs. Several worms with superficial penetration into the
mucosa. H&E
106
Table 14 Schematic life cycle of a hookworm
Oesophagus
t
...>-
L
C
(1) Trachea
coL
...u
0 t
Lungs
1-2 months
t
(1)
L
"'0
~ Venous
<:J
c:<lJ circulation
"tl
0
1 ..
:)
"tl
"<:
Larvae mature
to infection,
750l-lm in soil Maximum 6 weeks
23. UNCINARIASIS
Introduction
Hookworm infections are also called ancylostomiasis,
tunnel or miner's disease or necatoriasis. Uncinariasis is
a really important worm disease. Twenty to twenty-five
per cent of the world population, i.e. more than one billion
people, are carriers of hookworms. I n addition, it is a
dangerous worm disease, unlike many other helminthic
infections. In many countries, uncinariasis is a major
health problem; about 60 000 individuals die each year
from this helminthiasis. Mostly, children are affected.
Hookworm infections are found mainly in tropical
countries; Ancylostoma duodenale infection is also found
in countries with temperate climates. Necatoriasis is well
known in Venezuela, particularly in the rural population.
A different hookworm species affects cats and dogs
naturally, but it is not pathogenic for man, since, when
their larvae enter the human body, they do not mature or
migrate. Mice may be used for experimental studies 1 .
Clinically, at the site of entering the human body,
dermatitis (ground itch) may develop, sometimes persist-
ing for 2 weeks. A few hookworms do not cause disease;
however, a massive infection leads to continuous loss of
blood, severe anaemia and hypoproteinaemia, weakness
and retarded development in children. In the tropics,
uncinariasis is one of the important causes of immunode-
ficiencies and consequent opportunistic infections.
For a clinical diagnosis; numerous eggs of the hook-
worms can often be found in stools, or the stools may be
cultured. Fresh stool specimens should be handled with
care, because of the danger of infection for laboratory
personnel. Haematologically, a high eosinophilia may be
present.
The parasite
Several species of nematodes belong to the hookworms
and may produce uncinariasis. The two important hook-
worms are Ancylostoma duodenale which may be found
also in the Old World, and Necator american us, observed
only in the tropics. In addition, species of the genera
Trichostrongylus and Oesophagostomum may cause
uncinariasis. These worms are characterized by micro-
scopic structures similar to teeth or hooks at the oral
orifice. Structurally, there are no gross, but only minimal,
differences between Ancylomstoma duodenale and Nec-
HELMINTHIC DISEASES
• ~ if
Adults in
the intestine
1
Eggs in faeces
24-28 hours
1
Young larvae in
soil, 250 I-Im
ator americanus. Both are 1 cm long on average. Micro-
scopically, A. duodenale shows two pairs of fused curved
teeth at the mouth, and N. american us has two crescent-
shaped cutting plates (Figs. 23.1-23.5). The lifespan of
hookworms in the human intestinal tract may be many
years (without antihelminthic treatment). Eggs show
typical features, are colourless and have a thin shell. They
require a minimum temperature of about 18°C with
adequate humidity in order to stay alive. The eggs of both
species measure 60 x 40 .um.
Pathogenesis
Larvae are released from the eggs of hookworms in a few
days and penetrate man, after two moults, transcutane-
ously. Then, they begin to migrate; see the hookworm
type cycle in the general remarks on nematodiasis and
the schematic Table 14. A. duodenale may also enter man
orally. Mature worms, with their hook-like structures at
the mouth, actively destroy the mucosa of the small
intestine and suck blood. Occasionally, they may penetr-
ate into the submucosa and suck blood at these sites, i.e.
from the haemorrhages they themselves have caused.
With numerous worms in the intestinal tract, the continu-
ous loss of blood may be considerable.
Pathology
Dog or cat hookworms, penetrating transcutaneously,
may produce creeping eruption (cutaneous larva migrans)
in man; see Section 37.
During the migration of hookworm larvae (A. duodenale
or N. american us) in man, foci of eosinophilic infiltrates
may be found in the lungs. Often it is difficult to detect
larvae in these foci.
Mature hookworms in man are found in the jejunum or
ileum. They measure 1 cm on average, and are mostly
dark red or black because ofthe sucked blood (Fig. 23.6).
Other short intestinal nematodes, e.g. Strongyloides ster-
coralis, Enterobius vermicularis and Trichuris trichiura,
may be easily distinguished by their size, localization and
colour. Grossly, focal haemorrhages of variable extent may
be seen in the mucosa. As described above, hookworms
produce microscopic destructive lesions of the mucosa
of the small bowel when biting with their hooks, and may
penetrate into the submucosa (Figs. 23.7 and 23.8).
HELMINTHIC DISEASES 107

Fig. 23.1 Two Necator american us (mature worms) Fig. 23.2 Head of Ancylostoma duodenale

Fig. 23.3 Posterior part of an Ancylostoma duodenale female Fig . 23.4 Necator american us expelling eggs

•
Fig. 23.5 Balsa copulatrix of a male Ancylostoma duodenale Fig. 23.6 Small intestine with numerous dark hookworms and some
haemorrhages in the mucosa. Compare with Fig. 22.3
 108 HELMINTHIC DISEASES

Fig.23.7 Two horizontally cut hookworms in the haemorrhage of the Fig. 23.8 High power view of a horizontally cut hookworm encoun-
duodenal submucosa. H &E tered fortuitously in the wall of the duodenum. Same case as Fig. 23.7.
The sucked blood (erythrocytes) is seen clearly in the gut of the worm.
H&E

Fig. 23.9 Tiger heart'. i.e. fatty degeneration of the myocardium. in a

case of marked chronic anaemia in an infant in Venezuela. due to
hookworm parasitosis
HELMINTHIC DISEASES
The consequences of these intestinal injuries, with the
continuous loss of blood, may be severe. The resulting
chronic anaemia is of an hypochromic, microcytic and
iron-deficiency type 2-4. Previously, it was called chlorosis
or 'green sickness', particularly in adolescent females.
Fatty myocardial degeneration, due to chronic hypoxae-
mia, often leads to cardiac insufficiency and a fatal
outcome (Fig. 23.9).
Histologically, eosinophilic enteritis may be observed 5 .
Small intestinal mucosal biopsies do not reveal either
histological or enzymatic pathological changes 6 .
References
1, Wilkinson, M, J. et al. (1990). Necator americanus in the mouse:
histopathological changes associated with the passage of larvae
24. STRONGYLOIDIASIS
Introduction
Typical and special features of this worm infection are
the marked tissue lesions in the small. and sometimes in
the large, bowel which are often fatal. Strongyloidiasis is
a frequent intestinal parasitosis in the tropics. The worms
and their larvae require a mean temperature of at least
15°C for their development; this explains partly their
geographic distribution which is similar to that of hook-
worms. In some countries, 30-60% of people are infected,
and this worm infection has also been observed in miners.
I n Japan and South Europe, cases of this infection
are only reported occasionally. In Venezuela, this worm
disease is common.
Larvae of Strongyloides stercoralis from animal hosts
(dogs) enter man and cause creeping eruption, but
maturation and migration does not occur in man (as in
hookworms for animals). Other species of Strongyloides
are found in primates, rats and other mammals'.
Clinically, the infection may vary from being latent and
asymptomatic to massive infection with generalization. A
fatal outcome is not exceptional because of the picture
of malabsorption syndrome,
In immunocomprimised patients, cases of AIDS and
cortisone- treated patients, exacerbation of latent worm
infections is becoming increasingly important 2- 5. Sympto-
matology depends on the localization of the parasites;
symptoms are mostly those of enterocolitis.
Clinical diagnosis depends on the confirmation of free-
moving larvae in stools, Eggs are not always found in
stools. Larvae may also be looked for in aspirated material
from duodenum, in sputum and in urine. Also, small-
bowel biopsies should be considered as a diagnostic
tool 6 . Surprisingly, parasites can be detected in gastric or
duodenal biopsies when malignant tumours are sus-
pected. Blood eosinophilia might be absent in immuno-
suppressed patients. Stool cultures may also be used for
diagnostic purposes. For handling fresh stool specimens,
see Uncinariasis.
The parasite
Strongyloides stercoralis is also named Dwarf thread-
worm. The important parthenogenetic females of this
worm species reach only 2 mm in length in the intestinal
tract and are almost impossible to see with the naked eye.
The adult worms have a long life-span 7 . When they live
for many years in man, this may be due to the long life-
span or to continued auto-infection. Eggs are similar to
those of hookworms; they measure 55 x 30 j.tm.
109
through the lungs of mice exposed to primary and secondary infection,
Parasitol, Res" 76, 386 '
2, Layrisse. M. and Roche, M. (1964). The relationship between anemia
and hookworm infection, Results of surveys of rural Venezuela
population, Am. J. Hyg,. 79, 279
3, Roche. M, and Layrisse. M. (1966), The nature and causes of
hookworm anemia, Am. J. Trop, Med. Hyg.. 16. 1044
4, Martinez-Torres. C, et al. (1967), Hookworm and intestinal blood
loss, Trans, R. Soc. Trap. Med. Hyg., 61, 373
5, Croese, T. J, (1988). Eosinophilic enteritis - a recent North Queens-
land experience, Aust. N.Z J. Med.. 18. 848
6, Youssef. M, E, and Abou-Zakham. A. A. (1991), Some histopatholog-
ical and histochemical aspects of human ancylostomiasis, J. Egypt.
Soc, Parasitol., 21. 219
Pathogenesis
Man is the sole host. The possibilities for development
and infection are rather complicated:
1. Parthogenetic females lay eggs which hatch out as
larvae in the intestinal lumen of the host and pass out
in the faeces. In soil. the larvae become infectious
(Fig. 24,1) and may penetrate man transcutaneously
(direct development) going on to migrate through the
hookworm type of cycle
2. In addition to direct development (above), there may
also be indirect development, i,e. free-living female
and male worms may mate and produce eggs which
become fertilized. Later. larvae may penetrate man (see
above).
In summary, direct and indirect development lead
to percutaneous larval invasion. The larvae of S.
sterocora/is ma~ move through tissues at speeds up to
10cm per hour.
3. It is also possible to have endo- and exo-auto- (hyper)-
infection by endogenous Strongyloides larvae. Endo-
auto-(hyper)-infection takes place by penetration of
the mucosa by larvae which become infectious in the
intestinal lumen without reaching the exterior. This
occurs mostly in the colon, Exo-auto-hyper-infection
is the transcutaneous penetration of larvae which
derive, not from soil. but directly from the intestinal
tract of the host on the perianal skin, i.e. as in 1 and
2. but with a determined location of transcutaneous
penetration.
In addition to transcutaneous infection, oral infection by
food or water is possible but very rare. Transmission to
newborns via the mother's milk is said to be possible.
Worms and larvae invade the intestinal mucosa, The
larvae reach all layers of the intestinal wall, causing
inflammation. and become haematogenously generalized.
Pathology
The adult worms, 2 mm long, are almost invisible to the
naked eye, They are situated in the upper small bowel.
Grossly, in the small and large intestine. a marked
enterocolitis may be present with haemorrhages, necrotic
areas and ulcerations in the mucosa. Involvement of the
colon usually indicates a hyper or internal auto-infection.
Also. linitis plastica has been reported as due to strongylo-
idiasis 9 , as well as gastric strongyloidiasis imitating peptic
ulcer'o (Fig. 24.2).
Microscopically. adult worms and larvae may be found
 110 HELMINTHIC DISEASES

c
"

" y n
• co \)
" o

o
..
Fig. 24.1 Rhabditiform larva of Strongyloides stercoralis in a co pro- Fig. 24.2 Larvae and adults of Strongyloides stercoralis in a gastric
culture biopsy. H&E (Case of Dr Marcelo Mendoza. Merida)

Fig. 24.3 Numerous adult worms and larvae in the intestinal wall in
a case of a marked strongyloidiasis. low power. H&E

Fig. 24.4 Larvae of Strongyloides stercoralis in the intestinal mucosa.

H&E

Fig. 24.5 Larvae of Strongyloides stercora/is in the intestinal mucosa Fig. 24.6 Larvae of Strongyloides stercoralis in the intestinal mucosa
cut in several directions at high power. H &E cut transversally. H&E
HELMINTHIC DISEASES 111

Fig.24.7 Marked colitis in a case of autoinfection with Strongyloides Fig, 24.8 Larva of Strongyloides stercora/is in the lung with marked
stercoralis. H &E haemorrhagic inflammation. The larva is not easy to detect. H &E

Fig. 24.9 Larva of Strongyloides stercoralis in the lung, easy to Fig.24.10 Larva of Strongyloides in lymph node with marked eosino-
recognize without inflammatory reaction by the dark dots. H&E philic lymphadenitis. The microfilaria-like larva is easily recognized by
the dark dots. H & E

Fig. 24,11 Same lymph node as in Fig. 24.10. At high power Fig.24.12 Same lymph node as Figs. 24.10 and 24.11 . A transversally
eosinophilic lymphadenitis and, in the centre, a transversally cut larva cut larva of Strong/yoides stercora/is may be detected in the giant cell
of Strongyloides stercora/is may be seen. H &E on the left side. H & E
112
in the Lieberkuhn crypts and deeper. up to the submu-
cosa. Occasionally. it is difficult to differentiate between
them (Figs. 24.3-24.7). The larvae are recognized
because they show small dots and may be present in all
layers of the intestinal wall. Eggs are scarce and difficult
to detect in tissues. The tissue reaction consists mostly
of non-specific inflammation with lymphocytes. plasma
cells and leukocytes. Eosinophilic leukocytes are normally
scarce. When numerous eosinophilic leukocytes. giant
cells and granulomas are present. it appears that this
hypersensibility is due to endo-auto-hyper-infection. Lar-
vae may also be fou nd in skin 11. lungs (Figs. 24.8 and
24.9). Iiver12. lymph nodes (Figs. 24.10-24.12) and other
extra-intestinal sites; see Section 37.
References
1. Elangbam. C. S. et al. (1990). Strongyloidiasis in cotton rats
(Sigmodon hispidus) from central Oklahoma. J. Wild/. Dis.. 26. 398
2. Rogers. W. A. and Nelson. B. (1966). Strongyloidiasis and malignant
lymphoma. 'opportunistic infection by a nematode'. J. Am. Med.
Assoc.. 195. 685
25. TRICHINOSIS
Introduction
This disease is also called trichinellosis. Lesions caused
by the larvae of Trichinella spiralis are more important
than those caused by the mature worms. It is one of
the few parasitoses with high fever. Trichinosis has a
worldwide distribution in man and lower animals. It is
relatively common in the USA. Canada and Eastern
Europe. In Germany. trichinosis has been practically
eradicated by obligatory official meat inspection. How-
ever. in the eighties. an epidemic was reported in Germany
with more than 100 infected people 1. I n the tropics. the
prevalence appears to be low. Autochthonous infections
have not been reported in Venezuela.
This worm infection is known in almost all mammal
species. above all in rodents and wild animals. Domestic 2
and wild pigs are the main sources of human infection.
Mice and monkeys are used for experimental work 3- 6
Previously. epidemic outbreaks often occurred and a
fatal outcome was not exceptional. Lately. epidemics
have also been reported in Central Europe 7
Worm infection often is asymptomatic. There is a
gut trichinosis (caused by adult worms) and a muscle
trichinosis (caused by larvae). The first may show gastro-
enteritic symptoms with fever; the latter occurs with
muscle pain and swelling. signs of toxicity and allergy.
fever and oedema (eyelid). The fatal outcome is due to
pneumonia or cardiac failure.
For clinical diagnosis. mature worms and larvae may
be present in stools and larvae may be found in blood or
'in muscle biopsies. Eosinophilia is not always present.
During official meat inspections. larvae are found in
muscle samples microscopically. without staining and at
low magnification.
The parasite
Trichinella spiralis is the main causal agent. Another
species. T. pseudospiralis is of minor importance and
shows only minimal differences.
In the intestinal tract. the mature female worm measures
3-4 mm and the male 1.5 mm (Figs. 25.1 and 25.3). They
are difficult to see with the naked eye. The female is
viviparous and produces up to 1000-2000 larvae. The
latter measure from 100 pm to 1 mm.
3. Cruz. T. et al. (1966). Fatal strongyloidiasis in patients receiving
corticosteroids. N. Eng/. J. Med.. 275. 1093
4. Genta. R. M .. Miles. P. and Fields. K. (1989). Opportunistic
Strongyloides stercoralis infection in lymphoma patients. Cancer.
63.1407
5. Gompels. M. M. et al. (1991). Disseminated strongyloidiasis in
AIDS uncommon but important. AIDS. 5. 329
6. La Salle. R. et al. (1988). Strongiloidiasis duodenal. V. Congr. Ven.
Med. Int Barquisimeto
7. Grove. D. I. (1982). Treatment of strongyloidiasis with Thiabenda-
zole. an analysis of toxicity and effectiveness. Trans. R. Soc. Trop.
Med. Hyg .. 76. 114
8. McKerrow. J. H. et al. (1990). Strongyloides stercoralis: identifi-
cation of a protease that facilitates penetration of skin by the
infective larvae. Exp. Parasitol.. 70. 134
9. Lopez. J. E. (1988). Linitis plastica como manifestaci6n de Strong i-
loidiasis gastrica. v. Congr. Ven. Med. Int. Barquisimeto
10. Pruglo. I. V. el al. (1990). Gastric strongyloidiasis imitating peptic
ulcer. Arkh. Patol.. 52. 53
11. von Kuster. L. C. and Genta. R. M. (1988). Cutaneous manifestations
of strongyloidiasis. Arch. Dermato/.. 124. 1826
12. Lopez. J. E. el al. (1988). Strongiloidiasis hepatica. Presentaci6n
de un caso con confirmaci6n histopatol6gica. V. Congr. Ven. Med.
Int. Barquisimeto
Pathogenesis
Trichinella spiralis goes through the Trichinella type of
life cycle (see the general remarks under Nematodiasis).
The larvae are ingested by the host. mostly in raw meat.
They invade the mucosa of the small bowel (Figs. 25.3
and 25.4) where they develop8B The mature worms
have a short lifespan. The larvae may be disseminated
Iymphogenously or haematogenously. In the skeletal
muscle. they invade muscle fibres where they remain
viable for a long time. Inflammatory reaction is scarce
Later. a fibrotic capsule develops and calcification takes
place.
Pathology
Mature worms are found in the mucosa of the ileum. The
larvae are observed mostly in the muscle fibres of the
diaphragm. intercostal muscles. larynx. tongue and extra-
ocular muscles (Figs. 25.5-25.8). Muscles of the extremi-
ties are seldom involved. Exceptionally. the lungs and
central nervous system are affected. Trichinae are never
seen in the myocardium.
Non-specific inflammation around the larvae. arranged
in a spiral. is minimal. Later. calcified nodules with a
fibrotic capsule may develop; these are grossly visible.
References
1. Feldmeier. H. et al. (1984). Untersuchungen uber die Epidemiologie
der Trichinella-spiralis-Infektion in der Eifel 1982. Dtsch. Med.
Wschr. 109. 205
2. Cowen. P. el al. (1990). Survey of trichinosis in breeding and cull
swine. using an enzyme-linked immunoabsorbent assay. Am. J. Vet
Res. 51. 924
3. Antonios. S. N. el al. (1989). Experimental trichinosis in alloxan
induced diabetes in mice. J. Egypt Soc. Parasitol.. 19. 149
4. Brown. P. J. and Bruce. R. G. (1989). Kinetics of IgA plasma cells
in the intestine of NIH mice infected with Trichinella spiral is. Res.
Vet Sci. 46. 187
5. Jasmer. D. P. (1991) Trichinella spp.: differential expression of acid
phosphatase and myofibrillar proteins in infected muscle cells. Exp
Parasito/., 72, 321
6. Kumar. V. et al. (1990). Characterization of a Trichinella isolate from
polar bear. Ann. Soc. Belg. Med. Trap., 70. 131
HELMINTHIC DISEASES 113

Fig. 25.1 Mature female worm of Trichinella spira/is Fig. 25.2 Mature male worm of Trichinella spiralis

Fig. 25.3 Trichinella spira/is in the intestinal mucosa of a rat. H &E Fig.25.4 Trichinella spira/is in the musculature of a rat. H&E
 114 HELMINTHIC DISEASES

Fig.25.5 Larvae of Trichinella spira/is in human musculature. 10 days Fig. 25.6 Larvae of Trichinella spira/is in human musculature with
after infection. A case from the 1982 epidemic in Germany H&E marked inflammatory reaction. 4 weeks after infection. A case from the
1982 epidemic in Germany. H&E

Fig. 25.7 Larvae of Trichinella spira/is in human musculature with Fig. 25.8 Well developed larva of Trichinella spira/is in human tissue.
marked inflammation. 3 months after infection. Same 1982 epidemic as H&E
cases in Figs. 25.5 and 25.6. H&E
HELMINTHIC DISEASES
7. Ancelle, T. et al. (1986). The 1985 trichinosis outbreaks due to horse
meat in France. IX 1m. Congr Infect. Parasit. Dis. Muenchen. Abstr.
757
8. Wright. K. A. (1979). Trichinella spiral is: An intracellular parasite in
26. TOXOCARIASIS
Introduction
This worm infection is also called visceral larva migrans 1.
But. since this entity also may be considered under
other headings and another definition, it will be treated
separately in Section 37.
Toxocariosis is becoming increasingly important. The
number of pets in industrialized countries is increasing,
and 20% of all dogs, especially pups, are said to be
infected with Toxocara canis. The infection seems to
occur worldwide 2,3; children are most often affected,
frequently by playing in sand boxes or play grounds 4 , In
Venezuela, apparently, the consequences of this worm
infection are found frequently,
Do~s and cats are carriers of this nematode worm (Fig.
26,1 )6, more often young animals than older ones.
Man is a 'false' host. Pigs and mice may be used for
experimental purposes 7- 9 .
Clinically, in man, the lungs, eyes 10 and central nervous
system are the main or~ans to be involved and show
clinical symptomatology 1. Asthma, retinal detachment.
blindness and epilepsy are the main manifestations of this
worm infection.
For clinical diagnosis, persistent blood eosinophilia is
a key sign. Antibodies may be demonstrated by a series
of serological tests.
The parasites
Larvae of the nematode genus Toxocara (T. canis, T. cati)
are the causal agents. Their characteristics in tissues will
be discussed later See above, under Introduction.
Pathogenesis
Eggs are ingested, Their larvae become liberated within
the human gastrointestinal tract. They penetrate the inte-
stinal wall and move randomly in the foreign host.
However, their migration is blocked at some stage by
27. ANISAKIASIS
Introduction
This infection, caused by larvae of the genus Anisakis,
is also called herring worm disease. Its prevalence is
increasing; up to 1983, more than 1000 caseS had been
reported from Japan. Anisakiasis is found in countries
surrounding the North Sea and the Pacific Ocean. Most
cases have been reported from Japan 12 , the Netherlands
and England, and infection also occurs in tourists to these
places. Larvae of the herring worm, found in fish, caused
a lot of hysterical publicity in Germany a few years ago.
In Venezuela, no cases of this sort have been reported,
Natural definitive hosts are mammals from the sea, such
as dolphins, whales, seals 3 etc, Man is a 'false' host. Lab-
oratory animals may be used for experimental studies 45 .
Clinically, symptoms from the gastrointestinal tract may
be present. Obstruction of the small bowel may occur
due to stenosis and require surgery.
Clinical diagnosis: the complement fixation test and
skin test do not seem to be reliable tools, Duodenal
endoscopy may be useful in cases of gastric involvement.
115
the intestinal phase. J. Parasito!, 65, 441
9. Campbell, W C. (1988). Trichinosis revisited - another look at modes
of transmission. Parasito! Today, 4, 83
inflammation and granuloma formation. Maturation will
not be completed; the larvae die. Man, therefore, is a
'false' host. During migration, larvae may carry other
micro-organisms to various sites 12
Pathology
See Section 37.
References
1. Reotutar, R. (1990). Taking a close look at toxocariasis (news). J.
Am. Vet. Med Assoc, 196, 1009
2. Lamina, J. (1980). Larva-migrans-visceralis-Infektionen durch
Toxocara-Arten. Dtsch. Med Wschr., 105, 796
3. Gillespie, S. H. (1988). The epidemiology of Toxocara canis.
Parasito! Today, 4, 180
4. Dubin, S. et al (1975). Contamination of soil in two city parks with
equine nematode ova including Toxocara canis: A preliminary study.
Am. J. Pub! Health, 65, 1242
5. Barron, C. N. and Saunders, L. Z. (1966). Visceral larva migrans in
the dog. Patho! Vet (Basel), 3, 315
6. Parsons, J. C. et al. (1988). Disseminated granulomatous disease
in a cat caused by larvae of Toxocara canis. J. Camp. Pathol.. 99,
343
7. Done, J. T et al (1960). Experimental visceral larva migrans in the
pig Res. Vet. Sci, 1, 133
8. Parsons, J. C. and Grieve, R. B. (1990). Kinetics of liver trapping
of infective larvae in murine toxocariasis. J. Parasito!, 76, 529
9. Higa, A. et al (1990). Effects of Toxocara canis infection on
haemopoietic stem cells and haemopoietic factors in mice. Int. Arch.
Allergy App! Immuno!, 91. 239
10 Maguire, A. M. (1990). Recovery of intraocular Toxocara canis by
pars plana vitrectomy. Ophthalmology, 97, 675
11. Glickman, L. T. et al. (1979). Epidemiological characteristics and
clinical findings in patients with serologically proven toxocariasis.
Trans. R. Soc. Trap. Med Hyg., 73, 254
12. Frenkel, J. K., Dubey, J. P. and Miller, N. L. (1969). Toxoplasma
gondii: fecal forms separated from eggs of the nematode Toxocara
cati. Science, 164, 432
The parasite
Anisakis marina (Fig. 27.1), A. simplex and probably
other Anisakis species, may be causal agents. Recentlv,
Pseudoterranova decipiens, causing codworm anisakiasis,
has also been described in Japan and USA.
In herring and mackerel, the third stage larva is said to
reach 3 cm in length. For larvae in human tissues, see
Pathogenesis.
Pathogenesis
The ingestion of raw fish, above all herring, causes lesions
in the wall of the stomach and small bowel due to larvae
of the genus A nisakis , An allergic reaction is thought to
be responsible for these lesions.
The life cycle of these worms is not known completely,
It is thought that larvae of this kind must live in sea water.
The larvae, apparently, pass through several intermediate
animal hosts living in the sea. Definitive hosts seem to
be mammals which live in salt water. In man, as a 'false'
 116 HELMINTHIC DISEASES

Fig . 26.2 Embryonated egg of Toxocara sp.

Fig. 26.1 Mature adult worm of Toxocara sp. Fig. 27.1 Horizontal cut of an Anisakis marina worm. H&E

Fig.27.2 Anisakis marina worms in human tissue with marked inflam- Fig . 27.3 Higher power of a transversally cut Anisakis marina worm
matory reaction. H&E in human tissue. The oesophagus with a triangular lumen is clearly seen,
the same as the two typical fungus-like lateral cords. Beneath the
oesophagus the excretory organ is visible. H&E
HELMINTHIC DISEASES
host. the larvae of these worms do not become sexually
mature and do not complete migration and maturation.
They may be found beyond the gastrointestinal tract 6 .7 .
Pathology
The lesions in the antral region of the stomach wall and/or
in the small bowel wall consist of localized infiltrates
(Figs. 27.2 and 27.3) of eosinophilic leukocytes and
formation of eosinophilic granulomata. The localization in
the small intestine may lead to obstruction and stenosis8 .
When larvae are not found in tissues, the lesions are
believed to be due to an allergy. In the cases reported
from Japan, localization of lesions in the stomach prevails,
while, in cases from the Netherlands, the lesions are found
predominantly in the small bowel.
28. GNATHOSTOMIASIS
Introduction
This parasitosis is less important since it is geographically
limited, its prevalence is low and severe disease is not
common. The infection occurs practically only in Eastern 1
and South- East Asia 2 and in Oceania. Major endemic foci
have been reported from Thailand and Japan. The disease
is not known in Venezuela.
Normally, dogs, cats, wild felines and numerous other
lower animal species are infected and represent the normal
definitive hosts. Experimentally, rats, mice and monkeys
may be infected by giving them larvae orally3.
Clinically, a wide variety of symptoms may be present
since migration to any part of the body can take place 4 .5 .
The pattern observed is usually that of cutaneous or
visceral larva migrans (Section 37), but aetiological diag-
nosis of gnathostomiasis is difficult. The mortality rate is
high for gnathostoma encephalitis.
Clinical diagnosis is made by biopsy or when the worm
is surgically recovered or erupts to the surface of skin.
Eosinophilia is variable but generally not pronounced.
The parasite
Gnathostoma spinigerum is the most important of eight
species of this genus belonging to the group Spirurids.
Other members of this group include the nematodes,
Thelazia callipaeda. Gongylonema pulchrum, Physalop-
tera caucasica and Cheilospirura sp. (but only single
human cases of infection with the latter have been
reported).
Adult worms occur in man rarely; when they do, they
are sexually immature and ~ 1 cm long. The head bulb is
retractable and has rows of cuticular spines: the body is
covered in spines. The larvae of Gnathostoma spinigerum
in human tissues closely resemble the adult worms. The
entire body surface is covered by minute cuticular spines
(Fig. 28.1).
Pathogenesis
The ova of Gnathostoma spinigerum (Fig. 28.2) reach
the water in the excrement of meat-consuming hosts.
Larvae hatch from the eggs and reach, through two
intermediate hosts (crustaceans and fish, frogs or snakes),
other meat consumers, including man. Infection in man
is accidental: this parasite does not mature in man.
117
References
1. Asami, K. et al. (1965). Two cases of stomach granulomas caused
by Anisakis-like larvae nematodes in Japan. Am. J. Trap. Med Hyg.,
14.119
2. Yokogawa, M. and Yoshimura, H. (1967). Clinico-pathologic studies
on larval anisakiasis in Japan. Am. J. Trap. Med Hyg., 16, 723
3. Popov, V. N. et al. (1989). Anisakiasis in the Caspian seal. Parazitolo-
giia, 23, 178
4. Jones, R. E. (1990). Anisakis simplex: histopathological changes in
experimentally infected CBA/J mice. Exp. Parasitol.. 70, 305
5. Sakanari, J. A. and McKerrow, J. H. (1990). Identification of the
secreted neutral proteases from Anisakis simplex. J. Parasitol.. 76,
625
6. Sakanari. J. A. and McKerrow. J. H. (1989). Anisakiasis. Clin.
Micrabiol. Rev., 2. 278
7. van Thiel. P. H. and van Houten, H. (1967). The localization of the
herringworm Anisakis marina in and outside the human gastrointesti-
nal tract. Trap. Geogr. Med, 19, 56
8. Morlier. D. et al. (1989). A rare etiology of acute occlusion of the
small intestine: anisakiasis. Review of the literature apropos of a case.
Ann. Gastraenterol. Hepatol. Paris. 25. 99
Infection is acquired by eating parasitized raw 6 , fermented
or marinated fresh water fish or poorly cooked meat.
especially chicken and duck. The larvae penetrate the
wall of the digestive tract and move randomly into tissues
of internal organs and subcutis. They cause damage by
mechanical injury and toxic substances.
Pathology
Adult worms are found in nodules of the gastric wall in
meat consumers, including exceptionally man. The larvae
may reach practically all organs, and frequently the
subcutis. The organs preferentially involved are liver,
lungs, eyes, central nervous system, subcutis 7 , and, excep-
tionally, the breast8 .
The tissue reaction in thoracic and abdominal organs
has been studied mainly in experimentally infected anim-
als. In the lungs, pneumothorax has been observed due
to this worm infection; in abdominal organs, a tumour-
like swelling may result. Histologically, necrosis, haemor-
rhages and acute, non-specific inflammation with few
eosinophils have been described (Figs. 28.3 and 28.4).
In skin biopsies, a minor tissue reaction is common. When
the larvae become stationary, fibrosis and giant cells may
be observed.
References
1. Miyazaki, I. (1960). On the genus Gnathostoma and human gnatho-
stomiasis with special reference to Japan. Exp. Parasitol.. 9, 338
2. Daengsvang, S. et al. (1964). Epidemiological observations on
Gnathostoma spinigerum in Thailand. J. Trap. Med. Hyg., 67, 144
3. Koga, M. and Ishibashi, J. (1988). Experimental infection in a monkey
with Gnathostoma hispidum larvae obtained from loaches. Ann. Trap.
Med. Parasitol., 82, 383
4. Prijyanonda. K. B. et al. (1955). Pulmonary gnathostomiasis. a case
report. Ann. Trap. Med Parasitol.. 49, 121
5. Bovornkitti, S. and Tandhanand. S. (1959). A case of spontaneous
pneumothorax complicating gnathostomiasis. Dis. Chest.. 35. 1
6. Taniguchi. Y. et al. (1991). Comment in: J. Cutan. Pathol. 1991 Apr.:
18 (2): 65-6. J. Cutan. Pathol., 18, 112
7. Nagao. M. (1955). A case of creeping disease caused in man by a
larval Gnathostoma spinigerum. (Jap. text with Engl. abstract)
Fukuoka Acta Med, 46, 207
8. Tesjaroen, S. et al. (1990). A breast mass caused by gnathostomiasis:
brief report of a case. S.£. Asian J. Trap. Med. Publ. Health. 21, 151
 118 HELMINTHIC DISEASES

Fig. 28.1 Adult of Gnathostoma spinigerum in the human derm is

causing 'creeping eruption' similar to cutaneous larva migrans. H&E

Fig. 28.2 Typical ovum of Gnathostoma sp.

Fig.28.3 This structure in the subcutis near the larva of Gnathostoma Fig. 28.4 Marked leukocytic reaction around the Gnathostoma larva
spinigerum in Fig, 28.1 may represent a dead parasite. H&E of Fig . 28.1
HELMINTHIC DISEASES
29. ANGIOSTRONGYlOSIS
Introduction
Under this heading, two completely different parasitic
diseases are considered (A and B). Both are caused by
the same nematode genus, Angiostrongylus, and may
result in a fatal outcome. Two different species are
the causal agents, diverse organs are involved and the
infections occur in distinct geographical areas.
A is the Asiatic type of angiostrongylosis, found in the
region of the Pacific Ocean - India, China, South East
Asia and Australia l - 6 .
B is the American type, occurring in Central America,
the South of NorthAmerica, Colombia, Brazil and also in
Venezuela 7- 13 Six cases have been found in Merida and
could be examined histologically. The disease is observed
mainly in children.
In both A and B, the specific and definitive host is the
rat In A, cows, pigs, snails, crayfish, shrimp and captive
non-human primates 6 are also infected; in B, snails and
foals 14 Experimentally, A may be produced by infecting
monkeys; B by infecting rats.
Clinically, in A, there is a tropism for the parasites. They
are disseminated haematogenously and cause lesions in
the brain and meninges. In B, the ileocaecal region is
affected with tumour-like lesions which often require
surgery.
Clinical diagnosis is difficult in both types. In A, a skin
test is available for man; occasionally, parasites are found
in spinal fluid. Eosinophilia may be present in liquids and
in tissues. In B, intestinal biopsy is recommended for
clinical diagnosis 15 .
The parasite
Two of the sixteen species of Angiostrongylus are patho-
genic for man:
Causing A. Angiostrongylus cantonensis or Parastron-
gylus cantonensis, also called rat lung worm.
Causing B, Angiostrongylus costaricensis or Morera-
strongylus costaricensis.
In A, the rat is the specific host with 20-25 mm-Iong adult
worms in the pulmonary arteries. Snails are intermediate
hosts. Cow. pig, crab, crayfish, and shrimp are non-
specific hosts; man is an accidental host. In B, the rat is
the definitive host with parasites in the mesenteric arteries.
The rat is infected by snails. Also man is a definitive host
Pathogenesis
In A, human infection takes place by consumption of
infected intermediate hosts (shrimps and crustaceans).
The larvae penetrate the wall of the digestive tract and
reach, by haematogenous dissemination, the central ner-
vous system. Man is a false dead-end host.
In B, infection occurs by digestion of snails (intermedi-
ate hosts). The ova reach the ileocaecal region. Rat and
man are dead-end hosts.
Pathology
In A, larvae of A. cantonensis may be found at any site
but mainly in the central nervous system. Histologically.
proven cases are rare. The findings in experimentally
infected monkeys seem to be similar to those in man.
Grossly, abnormalities may be lacking. Microscopically,
119
a diffuse meningoencephalitis with dense infiltrates of
numerous eosinophils is found. Fragments of dead para-
sites may be surrounded by giant cells.
In human B infections, with Morerastrongylus costa-
ricensis, the terminal ileum, caecum, ascending colon and
appendix may be involved.
Grossly, inflammatory lesions with tumour-like enlarge-
ment and thickening of the wall of the intestine may
be seen, as well as obstruction with mechanical ileus.
Ulceration of the mucosa is common.
Histologically, ova, larvae and mature worms (they do
become sexually mature in man) may be encountered,
accompanied by diffuse infiltrates of eosinophils, lympho-
cytes, plasma cells and neutrophils. Additionally, a granu-
lomatous reaction, eosinophilic granuloma, vasculitis and
thrombosis may be observed.
Figures 29.1-29.6 illustrate Angiostrongylus can-
o
tonensis (A) in man; Figures 29.7-29.1 Angiostrongylus
costaricensis (B) in the rat and Figures 29.11-29.19
Angiostrongylus costaricensis (B) in man.
References
1. Alicata, J. E. (1965). Biology and distribution of the rat lungworm.
Angiostrongylus cantonensis and its relationship to eosinophilic
meningoencephalitis and other neurological disorders of man and
animals. Adv. Parasit. 3. 223
2. Alicata. J. E. and J indrak. K. (1970). Angiostrangylosis in the Pacific
and Southeast Asia. Thomas C C. Springfield
3. Beaver. P. C. and Rosen. L. (1964). Memorandum on the first report
of Angiostrongylus in man by Nomura and Lin. 1945. Am. J Trap
Med. Hyg.. 13, 589
4. Rosen. L. et aJ. (1967). Studies on eosinophilic meningitis. III.
Epidemiologic and clinical observations on Pacific Islands and the
possible etiologic role of Angiostrongylus cantonensis. Am. J
Epidemiol.. 85. 17
5. Punyagupta, S (1965). Eosinophilic meningoencephalitis in Thai-
land: Summary of nine cases and observations on Angiostrongylus
cantonensis as a causative agent and Pila ampullacea as a new
intermediate host. Am. J Trap. Med. Hyg.. 14. 370
6. Gardiner. D. H. et aJ. (1990). Eosinophilic meningoencephalitis due
to Anglostrongylus cantonensis as the cause of death in captive
non-human primates. Am. J Trap. Med. Hyg.. 42. 70
7. Morera. P. (1970). Investigaci6n del huesped definitivo de Angio-
strongylus costaricensis Bal. Chil. Parasit., 25. 133
8. Morera. P. and Ash. L. R. (1970). Investigaci6n del huesped
intermediario de Anglostrongylus costaricencis. Bol. Chil. Parasil..
25. 135
9. Morera, P. and Cespedes, R. (1971). Angiostrongylus costaricensls
n. sp. (Nematoda: Metastrongyloidea), a new lungworm occurring
in man in Costa Rica. Rev. BioI. Trap .. 18, 173
10. Zambrano. P. Z .. Diaz. P. I. and Salfelder. K. (1975). Ileocolitis
seudotumoral eosinofilica de origen parasitario. GEN (Caracas). 29,
87
11. Loria-Cortes, R. and Lobo-Sanahuja, J. F. (1980). Clinical abdomi-
nal angiostrongylosis. A study of 116 children with intestinal
eosinophilic granuloma caused by Angiostrongylus costaricensis.
Am. J Trap. Med. Hyg.. 29. 538
12. Malek. E. A. (1981). Presence of Angiostrongylus costaricensis
Morera and Cespedes 1971 in Colombia. Am. J Trap. Med. Hyg ..
30, 81
13. Salfelder. K. et aJ. (1970). Ileitis regional eosinofilica de origen
parasitario. GEN (Caracas). 25. 132
14. Wright, J. D. et al. (1991). Equine neural angiostrongylosis. Aust.
Vet. J, 68, 58
15. Fauza. D. de O. et al. (1990). Abdome agudo na infancia por
angiostrongiliase intestinal: relato de um caso. AMB Rev. Assoc.
Med. Bras. 36. 150
 120 HELMINTHIC DISEASES

Fig. 29.1 Two adult worms of Angiostrongylus cantonensis Fig.29.2 Young adult roundworm of Angiostrongylus cantonensis in
human brain tissue. H&E

Fig. 29.3 Adult Angiostrongylus cantonensis roundworm in human Fig.29.4 Larva of Angiostrongylus cantonensis in human lung tissue.
lung tissue. Testicle with spermatozoa is seen. H&E H&E

Fig.29.5 Two types of eggs of Angiostrongylus cantonensis in human Fig. 29.6 Egg of Angiostrongylus cantonensis in human lung tissue
lung tissue. H&E at high power. H&E
HELMINTHIC DISEASES 121

Fig.29.7 Numerous larvae and eggs of Angiostrongylus costaricensis Fig. 29.8 Larva of Angiostrongylus costaricensis in tissues of a rat.
in the intestinal mucosa of a rat. Experimental inoculation. H&E Experimental inoculation. H&E

Fig. 29.9 Ovum of Angiostrongylus costaricensis in tissue of a rat in Fig.29.10 Ovum of Angiostrongylus costaricensis of a rat in still later
later stage of evolution. Experimental inoculation . H&E stage of evolution. Experimental inoculation. H&E
 122 HELMINTHIC DISEASES

Fig. 29.11 Ileocaecal involvement of human Angiostrongy/us costa - Fig. 29.12 Another case of human Angiostrongy/us costaricensis
ricensis infection with marked thickening of the intestinal wa ll. A case infection from Merida. showing marked thickening of the intestinal wall.
from Merida. Venezuela Surgical specimen: resection because an intestinal cancer was suspected

Fig. 29.13 Several ova of Angiostrongy/us costaricensis in tissues of

the human cases of Figs. 29.11 and 29.12. H &E
HELMINTHIC DISEASES 123

Fig. 29.14 Adult worm of Angiostrongylus costaricensis in tissues of

the human cases in Merida. low power. H&E

Fig.29.15 Male Angiostrongylus costaricensisworm inhuman tissues.

high power. Testicle with spermatozoa is clearly visible. H&E

Fig.29.16 Angiostrongylus costaricensis with eosinophilic and gran- Fig. 29.17 Angiostrongylus costaricensis with eosinophilic tissue
ulomatous tissue reaction. H &E reaction and granuloma formation. H &E

Fig. 29.18 Angiostrongylus costaricensis. Eosinophilic and granulo- Fig. 29.19 Angiostrongylus costaricensis. Intestinal lesions with
matous reaction at high power. H&E vasculitis. H&E
124
30. CAPILLARIASIS
Introduction
Again, a nematodiasis of minor importance is produced
by two different species of a sole genus (A, Capillaria
hepatica and B, Capillaria philippensis). The species
occur in different geographical areas.
A has a large geographical distribution in the USA the
region of the Pacific Ocean, South Africa and South
America, but not in Europe 1- 5 , while B has been found
only in the Philippines 6- B Worm infections of this sort
have not been reported in Venezuela.
A is observed in numerous lower animal species
(rodents, mostly rats, and domestic animals) 10. B is seen
in fish and domestic animals.
Clinically, only a few fatal cases have been reported in
A, while, in B, epidemics with a high mortality rate have
been noted, accompanied by severe diarrhoea. Cardiac
failure and secondary infections were the causes of death.
Clinical diagnosis can be made only by biopsy of the
liver or small intestine.
The parasite
Structurally, this parasite is similar to the genus Trichinella,
at least regarding morphology of the oesophagus.
I n A, adult worms of Capillaria hepatica or Hepaticola
hepatica reach 2 cm in length and are very thin. The
typical ova, in the liver of the host reach the soil when
the host dies, via the decaying carcass. They then become
infective in the soil.
In B, the adult C. philippensis reaches only 5 mm in
length. The development cycle, through one or more
intermediate hosts, is unknown. The ova show charac-
teristic structures.
Pathogenesis
In A, infection takes place by ingesting ova from uncooked
livers of rodents or contaminated food and water. The
larvae hatch from the ova in the caecum and reach the
liver via the portal vein.
In B, people become infected by eating raw fish or
meat. The parasites penetrate into the mucosa of the small
bowel, causing inflammation n
31. DRACUNCULOSIS
Introduction
This threadworm infection, also called dracunculiasis or
dracontiasis, is widespread in endemic areas of Africa,
the Near East and Asia 1.2 . Millions of people were said to
be infected but the prevalence has reduced during recent
years. In Venezuela, autochthonous infections of this sort
are unknown.
Dogs, wolves and cats may be infected and serve as
reservoir hosts.
Clinically, during migration of the larvae in man (prepat-
ent period 10-14 months), symptoms may be lacking or
be of a non-specific or allergic type. One to four worms
may be present per patient.
Clinical diagnosis during migration may be made by an
indirect fluorescence method or skin test. Commonly,
eosinophilia is present. When the mature female long
worm appears on a ruptured skin blister, diagnosis is
easily made.
HELMINTHIC DISEASES
Pathology
In A, nodules up to 2-3 cm in diameter may be found in the
enlarged liver. Histologically, preserved or disintegrated
parasites and ova are present in large numbers. Abscess-
like foci, eosinophilic infiltrates and a marked granulomat-
ous reaction with numerous giant cells, are observed.
In B, only the mucosa of the small intestine is invaded
by the small nematodes; they do not penetrate into deeper
layers. The tissue reaction consists of a non-specific
inflammation with occasional eosinophils (Figs. 30.1-
30.3).
References
1. Ward, R. L. and Dent J. H. (1959). Capillaria hepatica infection in
a child, Bull. Tulane Med. Fac., 19, 27
2. Calle, S. (1961). Parasitism by Capillaria hepatica. Pediatrics, 27.
648
3. Garcia, F. R. et at. (1962). Eosinofilia elevada con manifestaciones
viscerales. Primer caso de infecci6n par Capillaria hepatica en
Mexico. Bol. Med. Hasp. Inf (Mex.) , 19, 179
4, Piazza, R.. Correa, M. A. and Fleury, R. V. (1963). Sobre um caso
de infestacao humana por Capillaria hepatica, Rev. Inst. Med. Trap.
S. Paulo, 5, 37
5. Kokai. G. K. et at. (1990). Capillaria hepatica infestation in a 2-
year-old girl. Histopathology, 17, 275
6. Chitwood, M. B. et at. (1968). Capillaria philippensis sp. n. (Nema-
toda: Trichinellida) from the intestine of man in the Philippines. J.
Parasitol.. 54, 368
7. Cabrera, B, D. et al (1968). Human intestinal capillariasis. III.
Parasitological features and management. Acta Med. Philippina, 4,
92
8. Detels, R. et at. (1969). An epidemic of intestinal capillariasis in
man, A study in a barrio in Northern Luzon. Am. J. Trap. Med. Hyg.,
18, 676
9. Whalen, G. E. et at. (1969). Intestinal capillariasis. A new disease
in man. Lancet, 1, 13
10. Brander, P. et at. (1990). Capillaria hepatica bei einem Hund und
einem Igel. Schweiz. Arch. Tierheilkd., 132, 365
11, Diaz, U. et al (1967). Human intestinal capillariasis. I. Clinical
features, Acta Med. Philippina, 4. 72
The parasite
Dracunculus medinensis, Medina, Guinea or Dragon
worm, is the longest threadworm in man. Mature male
worms reach 3-4 cm and females are up to 1 m long.
Males and females have different tail ends. The larvae of
D, medinensis (Fig. 31.1) are 0.5-1cm long with a
digestive tract. They reach drinking water and are eaten
by small crustacean species of the genus Cyclops, which
act as intermediate hosts. Two moults take place in these
copepods. Man or animals ingesting the small crustaceans
are the definitive hosts.
Pathogenesis
The minute Cyclops species (containing infective larvae
of D. medinensis) are ingested with the drinking water.
The larvae are liberated, penetrate the mucosa of the
duodenum and reach the bloodstream. During haema-
HELMINTHIC DISEASES 125

Fig. 30.1 Capillaria philippensis worms in the mucosa of the small

intestine with marked non-specific inflammation. H&E

Fig.30.2 Fragments of Capillaria philippensis worms in human tissue. Fig.30.3 Capillaria philippensis worm in the mucosa of small intestine
H&E at high power. H&E
126 HELMINTHIC DISEASES

togenous dissemination, maturation of the larvae takes
place. It is completed in the tissues of the subcutis where
copulation occurs with formation of new larvae.
Haematogenous migration until formation of mature
adult worms, and reproduction with formation of larvae
in the subcutis, takes about one year. The long female
worm may penetrate the skin and remain just under the
surface forming a blister after one month. When the blister
ruptures, the worm appears outside the body. The larvae
are liberated into the content of the blister, and, from
there, to a watery environment in order to be ingested by
the Cyclops species once more.
Pathology
During migration and before coming to the subcutis, the
larvae may cause encephalitis, pericarditis, lymphadenitis,
myositis, and may involve urogenital organs and other
sites 3- 7, causing abscesses which heal. leaving calcified
foci.
Skin lesions are found in legs and feet preferentially,
but also at other sites of the body. They may consist of:
palpable moving worms; cutaneous allergic reactions; or
a blister of 3-5 cm long which, after rupture, reveals a
long female worm (Fig. 31.2).
References
1. Ansari, A. R. and Nasir, A. S. (1963). A survey of guinea worm
disease in the Sind desert (Tharpaikar District) of West Pakistan.
Pakistan J Health. 13, 156
2. Elgart. M. L. (1989). Onchocerciasis and dracunculosis. Dermatol.
c/in., 7, 323
3. Kinare, S. G. et at. (1962). Constrictive pericarditis resulting from
dracunculosis. Br. Med. J, 1, 845
4. Lacombe, M. and Gentilini, M. (1963). A propos des localizations
intra-scrotales du verm de Guinee (Filaire de Medine). Presse Med"
71,1862
5. Reddy, C. R. R. M. and Valli, V. V. (1967). Extradural Guinea worm
abscess. Am. J Trap. Med. Hyg" 16, 23
6. Smith, D. J, and Sindique, F. H, (1965). Calcified Guinea-worm in
the broad ligament of a pregnant mother. J Obstetr. Gynaec. Br.
Comm., 72, 808
7. Verma, A. K, (1966). Ocular dracunculosis. J Ind. Med. Assoc., 47,
188

FILARIA INFECTIONS (Sections 32-35)

There are ten important worm species in the group of Table 15 Diagnosis of microfilariae
Filaria Wuchereria bancrofti, Brugia malayi, Brugia timon',
Loa loa, Onchocerca volvulus, Dirofilaria immitis, Dipeta- Schema of a microfilaria (shortened)
lonema perstans, Dipetalonema streptocerca, Mansonella
ozzardi and Microfilaria bolivariensis. Six of these filarial
worms produce more or less significant diseases, while
four are practically non-pathogenic for man. The diseases
are: filariasis caused by W bancrofti. B. malayi and B,
timori; loiasis by L loa; onchocerciasis by 0. volvulus; Sheath
and dirofilariasis by D. immitis.
D, perstans, D. streptocerca, M. ozzardi and M, bolivari-
ensis are widely distributed in Africa and South America Microfilariae with sheaths (in blood)
(M. bolivariensis in Venezuela), They are transmitted by
e·· ">
,
insects of the genus Culicoides (small midges) but do Wuchereria bancrafti 240- 3OO /lm
not lead to any serious disease. The microfilariae are
unsheathed. Brugia malayi 180-23O /lm ~=S
Filarial worms are very thin; the mature forms (adults
or macrofilariae) may be more than 10 cm long. The larvae Loa loa 250- 3OO /lm S-~.
of the filariae are called also microfilariae, reach 150- Mlcrofilariae without sheaths (in blood)
350l1m long and often cause more damage than the
mature worms. They may be found in lymphatic or blood
vessels, in the subcutis and, occasionally, in other organs
Dipetalonema perstans < 200/lm
--
"'i~

and tissues (larva migrans). Mansonella ozzardi 170-240/lm "31_.

Infection occurs through the bite of a blood-sucking
insect in which the microfilariae have reached maturation. Onchocerca volvulus 250- 33O /lm !'--- :::::0
They go through 4 moults. Man is the final host. Adults
measure from 1 cm (Loa loa) to 50-100 cm (D. volvulus).
In almost all cases of filarial infections, blood eosinophilia
Dipetalonema streptocerca 180-240/lm
~
Important: H&E stain is recommended for microfilariae. Giemsa stain
is present. Many infections remain asymptomatic. Ocular
and other techniques do not always stain the sheaths. especially in Loa
lesions are found in loiasis and onchocerciasis, and may loa. Microfilariae, when drying, lose their sheaths. either partially or
lead to blindness, totally.
For diagnosis of microfilariae, see Tables 15 and 16,

32. FILARIASIS
Introduction
This infection by three filarial species is called also
lymphatic filariasis or tropical elephantiasis, It is an
important disease, because many millions of people
are parasitized. Infection by Wuchereria bancrofti is
most frequent and occurs in tropical regions of Africa 1,
America 2,3, Asia 4 ,5. Australia and the Mediterranean
countries, They have been observed also in Venezuela,
Brugia malayi is limited to Southeast Asia and B. timori
to a small focus in Indonesia.
Dogs, cats and other animal species 6 have been found
to be infected with these species of filarial worms. Ferrets
are used for experimental purposes?
Clinically. microfilariae of these species may remain for
years in the blood of practically symptomless human
carriers. Mature worms may cause allergic reactions,
HELMINTHIC DISEASES 127

Fig. 31.1 First stage larva of Dracunculus medinensis Fig. 31.2 Adult female worm of Dracunculus medinensis perforating
the skin and appearing outside the human body

128
Table 16 Wuchereria bancrofti microfilaria from a thick blood smear,
stained with haematoxylin (Delafield),
a Congenital transmission is also known to occur.
a head, b multilolded 'sheath, c space within the succession of
nuclei nerve llI1g d area free of nuclei, e all
lymphangitis and lymphadenitis with hydrocele, elephan-
tiasis and chyluria.
For a clinical diagnosis, mobile microfilariae may be
seen in fresh blood samples taken at night and in fine
needle aspirates B For serological diagnostic methods 9 ,
see also Section 33,
The parasite
Adult worms of these three species have a nocturnal
periodicity, Wuchereria bancrofti reaches 10 cm long; the
other species are somewhat shorter,
Female filarial worms are ovoviviparous. The larvae are
coiled up in the ova situated in the uterus. When they are
released from the female. the larvae are liberated from the
eggs as microfilariae,
Microfilariae may be found in lungs and lymph nodes
of man. They are sheathed and measure 220-320 J.lm long
on average. They may be differentiated by the nuclei at
the end of the tail; see Tables 15 and 16 as well as Figs.
32.1-32.3.
Microfilariae are taken up in blood meals by mosquitos
of the genera Culex. Aedes. Mansonia and Anopheles.
In the insect. there are two moults before infective
microfilariae reach the labium of the mosquito.
Pathogenesis
When the mosquitos bite. the infective microfilariae burst
out ofthe labium and enter the human skin. The incubation
33. LOIASIS
Introduction
This infection with the filarial species (Loa loa) is limited
to Western Central Africa from Sierra Leone to Angola.
and occurs predominantly in the region of the great rivers.
The number of carriers of Loa loa is estimated at 20-40
million, Obviously. there are no autochthonous infections
of this kind in Venezuela.
Loiasis may occur in monkeys as reservoir hosts 1 .
Clinically. usually a mild disease is present. but its
manifestations may be severe 2 . An allergic swelling. which
may recur and cause severe itching. may be present, and.
in addition. marked pain in muscles and joints, as well as
conjunctivitis and blindness may be observed,
When making a clinical diagnosis. there is a marked
blood eosinophilia. In fresh blood drops, few microfilariae
may be found in the peripheral blood during the day time.
and 1-4 years after infection, This phenomenon of the
day and ni'ght periodicity of the filarial species has not
been elucidated satisfactorily.
HELMINTHIC DISEASES
period is 8-16 months. The prepatent period. i.e. the
development from the embryonic stage (microfilariae) to
sexually mature worms. is different for each species. The
filarial worms of these species have a tendency to situate
themselves inside lymph vessels.
Pathology
Grossly. splenomegaly and enlargement of lymph nodes
may be noted. The filarial worms are located in the
connective tissue. lymph vessels and lymph nodes (Figs.
32.4 and 32.5). and produce, due to obstruction of the
lymphatic vessels. chronic oedema and fibrosis leading
to elephantiasis of certain regions or organs. The latter is
often complicated by bacterial super-infection. Obviously.
in the tissues of long-standing elephantiasis. the parasites
are no longer found.
In lungs and lymph nodes. eosinophilic granulomas
caused by microfilariae may be observed. This feature is
also called tropical eosinophilic syndrome and belongs
to the larva migrans syndrome (Section 37).
References
1, Jordon. P. (1960). Epidemiology of Wuchereria bancrofti in Africa.
Indian J. Malarial.. 14, 353
2. Markell. E. K. (1964). Filarial infections in a Californian clinic. Ann.
Int, Med.. 61. 1065
3. Baird, J. K. and Neafie. R. C. (1988). South American brugian
filariasis: report of a human infection acquired in Peru. Am. J. Trap.
Med. Hyg.. 39, 185'
4. Liekian. J, et al. (1960). Wuchereria bancrofti infection in Djakarta.
Indonesia, A study of some factors influencing its transmission.
Indian J. Malarial.. 14. 339
5. Trent. S. (1963). Reevaluation of World War II veterans with filariasis
acquired in the South Pacific. Am. J. Trap. Med. Hyg., 12, 877
6. Hines, S. A. et a/. (1989). Lymphatic filariasis. Brugia malayi infection
in the ferret (Mustela putorius furo). Am. J. Path 01.. 134, 1373
7. Crandall, R. B. et al. (1990). Injection of microfilariae induces
resistance of Brugia malayi infection in ferrets and accelerates
development of Iymphostatic disease. Parasite-Immunol., 12, 229
8. Kapila, K. and Verma, K. (1989). Gravid adult female worms of
Wuchereria bancrofti in fine needle aspirates of soft tissue swellings.
Report of three cases. Acta Cytol.. 33, 390
9. Carvalho, P. A. etal. (1990). Evaluation of in vitro released Wuchereria
bancrofti third stage larval antigens for detection of bancroftian
filariasis. Trap. Med. ParasiL 41, 71
Serological and skin tests are only group specific (i.e.
for all species of filariae).
The parasite
Loa loa is also called migrating filaria. loa worm or eye
worm, Mature female worms of Loa loa are up to 70 mm
long and 0,5 mm wide; males are up to 35 mm long. Their
life-span may be 15 or more years. Adult worms are
thin. whitish. filamentous and cylindrical. The sheathed
microfilariae measure 275 x 7 J!m. The sheaths on the
microfilariae are better seen with H&E than with Giemsa
stain (Figs. 33.1 and 33,2), The larvae of Loa loa are
located in peripheral blood vessels during the day. They
are taken up by fly species of the genus Chrysops (mango
fly) in a blood meal. The microfilariae reach the thoracic
muscles of the fly and mature. passing finally into the
head in the region of the mouth.
HELMINTHIC DISEASES 129

Fig. 32.1 Microfilaria of Wuchereria bancrofti in blood smear. Note

tail without nuclei. Giemsa

Fig.32.4 Microfilariae of Brugia mala Vi in lymph node.

The dark dots are nuclei. H&E

Fig. 32.2 Microfilaria of Wuchereria bancrofti in blood smear. The

sheath is clearly visible. The dark dots are nuclei. H&E

Fig. 32.3 Microfilaria of Brugia malavi in blood smear. The sheath is

recognizable . H&E

Fig. 32.5 Eosinophilic lymphadenitis. One microfilaria of Brugia

mala Vi. transversally cut. surrounded by macrophages. H&E
130 HELMINTHIC DISEASES

".' .

Fig. 33.1 Microfilaria of Loa loa in a thick blood smear. The sheath is Fig. 33.2 Microfilaria of Loa loa; same case as Fig. 33.1 but with
clearly seen with this staining method. H&E another staining method. Here. the sheath cannot be recognized. Giemsa
HELMINTHIC DISEASES
Pathogenesis
During the bite of the Chrvsops fly, the microfilariae burst
out of the insect and enter the human skin. The incubation
period is usually several months. The development from
the microfilariae to mature worms of Loa loa takes from
1-4 years (prepatent period).
Pathology
The sexually mature worms of Loa loa may be found in
all parts of the subcutaneous connective tissue, but
preferentially at uncovered sites of the body. Live movin~
worms may be seen beneath the skin or conjunctiva.
They may cause oedema and swelling. Histologically, the
live worms cause non-specific inflammation with a few
giant cells and a fibroplastic reaction. A marked tissue
reaction usually is due to dead worms which also produce
chronic abscesses.
Microfilariae may be found occasionally at numerous
sites 4- 6 , such as central nervous system, spinal cord,
choroid and retina, lungs, myocardium, spleen and kid-
34. ONCHOCERCIASIS
Introduction
This filarial worm disease is also named river blindness.
In endemic regions, it represents a significant social and
economic problem. Onchocerciasis occurs in Central and
West Africa 1- 3 , the Nile Valley and Yemen; also in the
Caribbean region, Central America, Colombia and in the
North East of Venezuela 4
Some species of monkeys may be reservoir hosts.
Another species, Onchocerca armillata is found in cattle 5 .
Clinically, skin nodules are the typical manifestation of
this nematodiasis, but they are normally harmless and
may even be absent. Ocular lesions are a severe complic-
ation; the blindness rate in parasitic carriers is 10%.
For clinical diagnosis, microfilariae may be found in
small skin 'snips' taken from the areas surrounding the
skin nodules with bleeding 6 Sometimes, microfilariae
may be found in the urine. Eosinophilia is present as in
other worm infections.
The parasite
Onchocerca volvulus or O. caecutiens, a very thin filarial
worm, is the causal agent. The females are up to 70 cm
long and 0.4 mm wide but the males only up to 2-4 cm
long. Their lifespan is usually less than 10 years. The
microfilariae measure 250-330 flm in length and do not
have a sheath 7
The viviparous females may give birth to up to 1000
larvae or so-called microfilariae, daily (Fig. 34.1). Num-
erous species of Simulium flies (buffalo gnats or black
flies) are blood sucking and take up microfilariae with a
blood meal. If one fly takes up more than about 20
microfilariae, it will perish. Inside the fly, the microfilariae
develop and migrate to the mouth region where infective
microfilariae are found.
Pathogenesis
An infected gnat bites man and the microfilariae may
penetrate the skin. Here, mature worms develop producing
new microfilariae (larvae). Skin nodules may form 3-4
months after the bite. The prepatent period, from infection
until formation of new microfilariae, is 12-15 months.
131
neys. Usually, eosinophilic granulomas are seen, similar
to those in visceral larva migrans (Section 37).
References
1. Duke, B. 0 L. and Wijers, D. J. B. (1958). Studies on loiasis in
monkeys. I. The relationship between human and simian Loa in the
rain-forest zone of the British Cameroons. Am. Trop. Med. Parasit.,
52, 158
2. Noireau, F. et al. (1990). Clinical manifestations of loiasIs in an
endemic area in the Congo. Trap. Med. Paras/t, 41. 37
3. Pinder, M. et al. (1988). Identification of a surface antigen on
Loa loa microfilariae the recognition of which correlates with the
amicrofilaremlc state in man. J immuno/., 141, 1480
4. van Bogaert, L. et al. (1955) Encephalitis in Loa loa filariasis. J
Neura/. Psychiatr., 18, 10
5. Morel, L. et al. (1967). Infiltrats pulmonaires eosinophiliques au
cours de filarioses de type Loa-loa. Poumon Coeur. 23, 685
6. Toussaint, D. and Danis, P. (1965). Retinopathy In generalized Loa-
loa filariasis. A clinico-pathological study. Arch. Ophtha/. (Chicago),
74, 470
Male worms and microfilariae may wander in dermis and
subcutis and do not always form nodules.
Adult worms are of less clinical significance than
microfilariae. The latter may invade the cornea of the eyes,
causing damage to all parts of the ocular bulb and thus
lead to blindness B
Pathology
Cutaneous lesions. Typical lesions are palpable nodules
in the skin, also called onchocercomas. They may be
found on the trunk, head and shoulders or at other
sites 910 In each country or region, a different or specific
localization of onchocercomas may prevail. Up to 50
nodules may be present in one patient. In each nodule,
several mature worms may be present and when the
nodules perforate or break up, loops of thin worms may
be seen. In addition to the typical nodular lesions in the
skin, there may be eczema-like, sclerodermiform and
hypo- or depigmented cutaneous lesions.
Histologically, in the nodules, three zones may be
distinguished:
1. A fibrous capsule on the periphery with few cells and
numerous collagen fibres.
2 A non-specific granulation tissue with infiltrates of
neutrophils, eosinophils, lymphocytes, plasma cells
and histiocytes in variable amounts.
3. A central region where adult worms are situated coiled
up; thus, they will be cut in various directions. Also
microfilariae are found in these regions. Histiocytes,
epithelioid cells and multinucleated giant cells may
be seen. Adult worms may be examined by special
methods 1112 (Figs. 34.2-348).
Older nodular lesions show more fibrous tissue. Cellular
infiltrates and microfilariae may also be present outside
the onchocercomas. Active inflammation is found mostly
after the microfilariae have died.
Summarizing, microfilariae are found in the uteri of the
worms, free in the surrounding tissues and, occasionally,
in the peripheral blood. There is no periodicity as in other
filarial worm infections. Microfilariae may survive in the
skin for 6-10 months.
 132 HELMINTHIC DISEASES

Fig. 34.1 Cluster of young larvae (microfilariae) of Onchocerca vol-

vulus in smear of the cut surface of a fresh nodule in the skin. H &E

Fig. 34.4 Microfilariae of Onchocerca volvulus in an adult female

worm. H&E

Fig. 34.2 Onchocerciasis. Microfilariae of Onchocerca volvulus are

difficult to recognize in the dermis at this magnification. H&E

Fig. 34.3 Onchocerca volvulus worms in skin nodule containing

microfilariae. Low power. H&E

Fig.34.5 Female Onchocerca volvulus worm in skin nodule showing

eggs. H&E
HELMINTHIC DISEASES 133

Fig. 34.6 Adult Onchocerca voluvlus filaria in skin lesion. cut in

another direction . H&E

Fig. 34.7 Microfilariae of Onchocerca volvulus in skin lesion with Fig. 34.S Microfilariae of Onchocerca volvulus in skin lesion at high
scarce inflammatory reaction. H&E power. H&E
134
Ocular lesions. These are due to invasion of micro-
filariae. They may be found microscopically, as livin~
micro-organisms, as dead ones or as fragments 13- 1 .
Features which may be present include oedema of the
eyelids, conjunctivitis, keratitis and panophthalmitis in
different stages of evolution. The inflammatory reaction
will be more marked when the microfilariae are dead.
References
1. Albiez, E. J. et al. (1984). Studies on nodules and adult Onchocerca
volvulus during a nodulectomy trial in hyperendemic villages in
Liberia and Upper Volta. II. Comparison of the macrofilaria popu-
lation in adult nodule carriers. Trapenmed. Parasit.. 35, 163
2. De Sole, G. (1990). Migration studies in the onchocerciasis con-
trolled areas of West Africa. Trap. Med. Parasit., 41, 33
3. Vuong, P. N. et al. (1988). Forest and savanna onchocerciasis:
comparative morphometric histopathology of skin lesions. Trap.
Med. Parasitol., 39, 105
4. Botto. C.. Arango. M. and Yarzabal, L. (1984). Onchocerciasis
in Venezuela: prevalence of microfilaraemia in Amerindians and
morphological characteristics of the microfilariae from the Upper
Orinoco focus. Trapenmed. Parasit. 35, 167
5. Mtei. B. J. and Sanga, H. J. (1990). Aortic oncocercosis and
elaeophorosis in traditional TSZ-cattle in Tabora (Tanzania) preva-
35. DIROFILARIASIS
Introduction
Dirofilariasis, also called human zoonotic filariasis, is
another filarial worm infection of minor importance; only
sporadic reports of human dirofilariasis exist.
Worm infections of this sort have been found in South-
ern Europe, the Eastern Mediterranean countries and the
USA. mainly in the southern regions 1 . Infection is also
known in Venezuela. One human case has been reported
from Merida 2 ; this was a fortuitous finding at autopsy.
In numerous cases of human dirofilariasis, diagnosis is
not confirmed; other filarial worms are discussed as
possible causative agents.
There is a large animal reservoir of hosts, mostly
domestic animals, such as dogs 3 and cats, but also wild
carnivores from allover the world. Dogs and cats may be
used for experimental work 4- B Aedes aegvpti has been
found to transmit microfilariae to dogs 9 .
Few human cases are known. They show subcutaneous
or conjunctival nodular lesions, or pulmonary and cardio-
vascular involvement. with variable and non-specific
symptoms. In some cases, 'coin lesions' have been found
in the lungs with X-ray
Clinical diagnosis has been made mostly by examin-
ation of surgical specimens. ELISA has been found lately
to be useful for diagnosis1O.
The parasite
Dirofilaria immitis is also called dog heartworm. This
species is found mainly in cases with involvement of
viscera, while, in cases of cutaneous lesions, other species
of the genus Dirofilaria are observed (D. tenuis, D. repens,
D. conjunctivae).
The morphology of adult worms has not been studied
completely because only dead worms, fragments of them
or immature parasites have been examined in tissues.
Female worms have been found to reach 10 cm in length,
contain unfertilized ova, and also microfilariae in the
uterus. A characteristic feature seems to be the thick
laminated cuticle of the adult worms with spines.
The cycle of development of these filarial species is
unknown. Man seems to be a false unsuitable dead-end
HELMINTHIC DISEASES
lence and pathology. Vet. Parasito/., 36, 165
6. Rivas Alcala, A. R. et al. (1990). Correlaci6n entre oncocercomas y
positividad para microfilarias en oncocercosis. Salud Publica Mex..
32, 658
7. Eichner, M. and Renz, A. (1990). Differential length of Onchocerca
volvulus infective larvae from the Cameroon rain forest and savanna.
Trap. Med. Parasit.. 41. 29
8. Duke. B. 0 (1990). Human onchocerciasis - an overview of the
disease. Acta Leiden. 59, 9
9. Guderian, R. H. and Kerrigan, K. R. (1990). Onchocerciasis and
acquired groin hernias in Ecuador. Trap. Med. Parasit.. 41, 69
10. Albiez, E. J. and Buettner. D. W (1984). Corium attached onchocer-
comata clinical and histological findings. Zb/. Bakt. HVg. A., 258,
388
11. Duke, B. O. (1990). An improved method of examining adult
Onchocerca volvulus worms. Trap. Med. Parasitol.. 41, 25
12. Duke, B. O. et al. (1990). On the reproductive activity of the female
Onchocerca volvulus. Trap Med. Parasitol., 41, 387
13. Semba, R. D. et al. (1990). Longitudinal study of lesions of the
posterior segment in onchocerciasis. Ophthalmologv, 97, 1334
14. Rothova, A. et al. (1990). Ocular involvement in patients with
onchocerciasis after repeated treatment with ivermectin. Am. J.
Ophthalmol., 15, 110
15. Newland, H. S. et al. (1991). Ocular manifestations of onchocerci-
asis in a rain forest area of west Africa. Br. J. Ophthalmo/.. 75, 163
host. Mosquitos (Aedes, Anopheles, Culex) and fleas are
carriers, vectors or intermediate hosts.
Pathogenesis
Details of transmission and infection are not available.
When isolated parasites have been found, they have been
young. Free microfilariae have not been found in tissues
of man, only in blood (Fig. 35.1).
Pathology
Cutaneous lesions. Nodular subcutaneous lesions are
present at various sites and also in the conjunctiva.
Subjacent musculature and bones are not usually
involved. The nodules reach 1-6 cm in diameter. Only
once, has more than one parasite been found in a nodule.
Nodular lesions have also been reported in lymph nodes
Pulmonary and cardiovascular lesions. Grossly,
infarct-like foci have been noted in the lungs. Female
worms are usually noted in pulmonary arteries, the inferior
vena cava, cardiac cavities and peripheral arteries. Imma-
ture and dead worms, larger than microfilariae, are situated
coiled up in thrombotic masses; they are seen cut in
various directions. At these sites, parasites are found
rarely and usually fortuitously in surgical or autopsy
specimens (Figs. 35.2-35.7). The structural details of
the worm's cuticle leads to diagnosis. An eosinophilic
pneumonia is noted surrounding the intra-arterial para-
sites and sometimes a foreign body reaction is seen (Fig.
35.8).
References
1. Risher, W H. et al. (1989). Pulmonary dirofilariasis. The largest
single-institution experience. J. Thorac. Cardiovasc. Surg., 97, 303
2. Salfelder, K., de Arriaga, A. D. and Rujano, J. J. (1976). Caso
humano de dirofilariasis pulmonar. Acta Med. Venezo/., 23, 87
3. Ward, J. W (1965). Prevalence of Dirofilaria immitis in the heart of
HELMINTHIC DISEASES 135

Fig. 35.1 Microfilaria of Dirofilaria immitis in blood smear. H&E Fig. 35.2 Adult Dirofilaria immitis filaria in a lung focus surrounded
by numerous leukocytes. Human case. H&E

Fig. 35.4 Four filariae of Dirofilaria immitis in a pulmonary artery.

Human case. H&E

Fig.35.3 High power of Fig. 35.2 . H&E

136 HELMINTHIC DISEASES

Fig. 35.5 Adult filaria of Dirofilaria immitis in a human lung at high Fig.35.6 Transversally cut Dirofilaria immitis filaria in human pulmon·
power. H&E ary artery with Hoeppli-Splendore phenomenon. H&E

Fig.35.7 Deformed filaria of Dirofilaria immitis. longitudinally cut. in Fig . 35.S Foreign body reaction near filaria of
a lung focus. H&E Dirofilaria immitis in a human lung. H&E
HELMINTHIC DISEASES
dogs examined in Mississippi. J. Parasit., 51, 404
4. Eaton, K. A. and Rosol, T. J. (1989). Caval syndrome in a Dirofilaria
immitis-infected dog treated with dichlorvos. J. Am. Vet. Med.
Assoc., 195, 223
5. Ludders, J. W. et a/. (1988). Renal microcirculatory and correlated
histologic changes associated with dirofilariasis in dogs. Am. J. Vet.
Res., 49, 826
6. Grauer, G. F. et a/. (1989). Experimental Dirofilaria immitis-associ-
ated glomerulonephritis induced in part by in situ formation of
immune complexes in the glomerular capillary wall. J. Parasito/., 75,
585
36. RARE AND UNCOMMON NEMATODIASES
Six roundworm infections have been reported In man
rarely and/or in limited geographical areas,
Acanthocephaliasis
Moniliformis moniliformis and Macracanthorhynchus
hirudinaceus belong to the class Acanthocephala or
thorn- head worms of nematodes, They have a retractable
head with thorn-like recurved spines and attack the
digestive tract. They are found only occasionally in man
in the Far East and South East Asia 1. There were only
nine recorded human infections with M. hirudinaceus in
Thailand up to 1989 2 ,
Dioctophymatosis
Dioctophyma renale, the giant renal worm, is a round-
worm, the female being up to 1 m long. This infection
has been reported in Europe, Asia and the Americas. The
renal pelvis and the abdominal cavity may be invaded by
the adult worm. Carnivorous animals may be infected.
Lagochilascariasis
Lagochilascaris minor is a roundworm species in which
the females measure up to 1.5 cm in length. Human
infection is limited to the Caribbean region. Draining
subcutaneous abscesses are formed. It is possible that
the reservoir hosts are wild animals with intestinal infec-
tions 3- 5 .
M icronemiasis
Micronema deletrix is a free-living saprophagous round-
worm. The adult worms have the dimensions of a microfi-
laria. One human case with meningo-encephalomyelitis
has been reported and infection is known in horses 6- B
Oesophagostomiasis
Several species of the genus Oesophagostomum may
infect man, Female worms are up to 22 mm long. Human
cases have been found in Brazil. Indonesia and tropical
Africa. The caecum and large intestine are involved.
Infection occurs through contaminated food and water.
Domestic animals and simians may also be infected 9- 11 .
Trichostrongyliasis
Eight species of the genus Trichostrongylus are patho-
genic for man. Infections are generally encountered in
137
7. Sasaki, Y. et al. (1990). Improvement in pulmonary arterial lesions
after heartworm removal using flexible allegator forceps. Nippon
Juigaku Zasshi, 52, 743
8. Rawlings, C. A. et a/. (1990). Morphologic changes in the lungs of
cats experimentally infected with Dirofilaria immitis. Response to
aspirin. J. Vet. Intern. Med., 4, 292
9. Hendrix, C. M. et a/. (1986). Natural transmission of Dirofilaria
immltis by Aedes aegypti. J. Am. Mosq. Contral Assoc., 2, 48
10. Sato, M. et al. (1985). Human pulmonary dirofilariasis with special
reference to the ELISA for the diagnosis and follow-up study. Z.
Parasitenkd., 71, 561
the warm countries of the Near East Africa and Asia; the
prevalence of human infection varies considerably but
millions of cases are estimated worldwide. Infection takes
place orally via contaminated food and water or migration
like the hookworms and the adult worms measure up to
9 mm. Domestic animals. especially ruminants. may be
infected. The digestive tract is affected, but with relatively
little clinical significance. Poisoning of the host by meta-
bolic products of the parasite may occur in severe infec-
tions 12- 1n
References
1. Zhao. B. et al. (1990). Licht-und elektronenmikroskopische Unter-
suchungen zur Histopathogenitiit von Macracanthorhynchus hiru-
dinaceus in experimentell infizierten Hausschweinen. Parasito/. Res..
76. 355
2. Radomyos. P. eta/. (1989). Intestinal perforation due to Macracan-
thorhynchus hirudenaceus infection in Thailand. Trap. Med. Parasit..
40. 476
3. Draper. J. W. (1963). Infection with Lagochilascaris minor. Br. Med.
J.. 1. 931
4. Little. M. D. (1964). Life cycle of Lagochilascaris minor. J. Parasit..
50. 34
5. Oostburg. B. F. J. and Varma. A. A. O. (1968). Lagochilascaris
minor infection in Surinam. Am. J. Trop. Med. Hyg.. 17. 548
6. Ferris. D. H. et a/. (1972). Micronema deletrix in equine brain. Am.
J. Vet. Res.. 33. 33
7. Hoogstraten. J. and Young. W. G. (1973). Meningo-encephalitis
due to the saprophagous nematode Micronema deletrix. Can. J.
Neural. Sci.. 2. 121
8. Rubin. H. L. and Woodward. J. C. (1974). Equine infection with
Micronema deletrix. J. Am. Vet. Med. Assoc.. 165. 256
9. Haaf. E. and van Soes!. A. H. (1964). Oesophagostomiasis in man
in North Ghana. Trap. Geogr. Med.. 16. 49
10. Anthony. P. P. and McAdam. I. W. (1972). Helminthic pseudo-
tumours of the bowel: thirty four cases of helminthoma. Gut. 13. 8
11. Chang. J. and McClure. H. M. (1975). Disseminated oesophagosto-
miasis in the rhesus monkey. J. Am. Vet. Med. Assoc. 167. 628
12. Biocca. E. et al. (1960). Further studies on Trichostrongyliasis in
Jewish communities in Iran. Parasitology. 2. 345
13. Tejada. A. and Burstein. Z. (1964). Primer caso aut6ctono de
trichostrongylosis en Peru. Bo/. Chi/. Parasito/., 19. 125
14. Markell. E. K. (1968). Pseudo hookworm infection - Trichostrongy-
liasis. N. Eng/. J. Med.. 278. 831
15. Sabka et a/. (1967). Intestinal helminthiasis in the rural area of
Khuzestan. South West Iran. Am. Trap. Med. Parasitol.. 61. 352
16. Lawless. D. K. et a/. (1956). Intestine parasites in an Egyptian village
of the Nile Valley with emphasis on the Protozoa. Am. J Trap. Med.
Hyg. 5. 1010
138
37. lARVA MIGRANS
Two definitions have been proposed for this clinical
entity:
1. The presence of larvae in tissues of a 'false' host or
infection due to larvae which do not mature in man.
Aberrant nematode larvae may move aimlessly for a
prolonged time; are not able to reach sexual maturity
in man and are not transmitted further. Man is infected
fortuitously, being a 'false' dead-end host. This group
also includes worms which become mature, but the
eggs or larvae remain in the tissues or the intestine
and are not excreted. Apart from the skin, the liver.
lungs. central nervous system and eyes are the main
organs to be involved. but other organs and tissues
may be affected. Larvae of the species of the genera
Toxocara, Am·sakis and Angiostrongylus may behave
in this way. It is admitted that larvae of the nematode
genera. Strongyloides, Dirofilaria and Gnathostoma.
cause a similar clinical picture.
2. The often fortuitous finding in tissues of larvae whose
species cannot be determined on morphological
grounds.
By this definition, larva migrans includes all cases
of larvae. microfilariae. or fragments of them. in human
tissue. in which histological diagnosis of the worm
species is impossible to make. In a case of microfilariae
of filarial worms in tissues. for instance. it cannot often
be determined whether or not they possess sheaths. a
feature which allows classification. Thus, this defini-
tion is of practical significance for pathologists.
Two clinical entities are considered: cutaneous LM and
visceral LM.
Cutaneous larva migrans (creeping eruption)
This localization of migrating larvae or microfilariae is
found mainly in the tropics or sUbtropics 1 . The wandering
larvae in the superficial layers of the skin do not commonly
get into the circulation nor do they invade viscera.
The best known agents of creeping eruption are the
canine hookworms. Ancylostoma braZl·liense and A. can-
inum. On the feet hands or any other part of the body. a
slight irritation results with papules and linear skin lesions
(Fig. 37.1). These mark the route of the larvae and may
be infected secondarily. They are active for up to a few
weeks only advancing 3-5 cm per day. and then they die.
The larvae of human hookworms. Strongyloides, Gna-
thostoma and the microfilariae of filarial worms. also may
cause creeping eruption 2- 4
A picture similar to cutaneous larva migrans is called
'swimmer's itch'. but. in this infection. there is no migra-
tion. Cercariae of trematode species produce the cercarial
dermatitis. and sparganum stages of fish tapeworm spec-
ies cause sparganosis. Fly larvae may provoke cutaneous
myiasis.
Visceral larva migrans
Introduction
When infection with larvae of the genera. Toxocara,
Anisakis, Angiostrongylus or others. can be demonstrated.
the disease should be named toxocariasis or after the
name of the causal nematode. The denomination visceral
larva migrans is better reserved for cases without an exact
diagnosis of the species of worm.
Visceral larva migrans occurs worldwide. but preferenti-
ally in tropical countries. In Europe and North America. an
increasing number of pets (dogs and cats) is maintained in
HELMINTHIC DISEASES
urban centres and this. possibly. is the reason why an
increasing number of cases of visceral larva migrans is
reported in these parts. Mostly infants are affected.
Clinically. hepatomegaly. pulmonary disorders and
symptoms like asthma. pyrexia. granulomatous ophthal-
mitis 5, retinal detachment and blindness. and epilepsy.
may be due to visceral larva migrans.
Clinical diagnosis: almost always a high blood eosino-
philia is present. Serological tests may be useful.
The parasite
In addition to larvae of the above-mentioned genera.
those of Ascaris lumbricoides, Strongyloides, Capillaria
hepatica, Trichostrongylus spp. filarial worms and species
of Pentastomida and Spirometra. belong to this group.
since. when found in tissues. species diagnosis cannot
be made on structural grounds. Exceptionally. Trichuris
vulpis may cause visceral larva migrans 6
Pathogenesis
Visceral LM occurs when the larvae or microfilariae
of filarial worms do not follow their normal cycle of
development but wander around and come to organs and
sites out of their usual way. There. they may be blocked
by an inflammatory reaction with granuloma formation.
The larvae may still be visible in these lesions, they may
have disappeared, following their migratory route. or they
may have disintegrated after producing the inflammation.
Migrating nematode larvae may spread micro-organisms.
Pathology
The damage caused by visceral larva migrans IS more
pronounced than that resulting from the creeping erup-
tion. Grossly. miliary granulomas may be seen in the
viscera. The localization of tissue lesions is fortuitous.
and they may be found in several organs of a single
person (Figs. 37.2-37.6).
The following entities belong more or less to the disease
under discussion.
1. Allergic granulomas with manifestations in several
organs 7- 11 .
2. Loeffler syndrome is due to larvae of Ascaris lumbri-
coides in the lungs which cause fast-vanishing infil-
trates of eosinophilic leukocytes. After a few days,
these are invisible to X-ray and are found only fortuit-
ously at autopsy.
3. Tropical pulmonary eosinophilia (TPE) and the
syndrome of Meyers-Koumenaar may be due to
filariasis with granulomas in liver. spleen and lymph
nodes.
4. Visceral eosinophilic granulomas. in various
organs. also possibly belong to this group of
lesions 12 .13 Larvae or microfilariae are usually no longer
seen in these granulomas (see Pathogenesis) (Figs
37.7-37.9). The latter. however. for instance in the
liver. may also be produced by ova of Schistosoma or
by other parasites.
References
1. Scheiner. R. B. et at. (1990). Lesions on the feet of a scuba diver.
Cutaneous larva migrans. Arch. Dermatol.. 126. 1092
2. Caplan. J. P (1949). Creeping eruption and intestinal strongyloidi-
asis. Br. Med. J.. 1. 396
3. Nagao. M. (1955). A case of creeping disease caused in man by a
larval Gnathostoma spinigerum. Fukuoka Acta Med.. 46. 2013
HELMINTHIC DISEASES 139

Fig. 37.1 Cutaneous larva migrans ('creeping eruption').

Fig.37.2 Visceral larva migrans in the myocardium with foreign body

giant cell and focal inflammation. H &E

Fig.37.3 The same case as Fig. 37.2 at medium power. H&E Fig.37.4 The same case as Figs. 37.2 and 37.3. The microfilaria-like
larva is clearly visible at high power. H &E
140 HELMINTHIC DISEASES

Fig. 37.6 Larva migrans with focal inflammation in the wall of the
duodenum . The necrobiotic larva is faintly seen in the upper part. H&E

Fig.37.5 Granuloma due to larva migrans in the mesocolon. The larva Fig.37.7 Visceral eosinophilic granuloma with central necrosis in the
is not seen at this magnification. H&E liver. probably due to visceral larva migrans. H&E

Fig.37.8 Visceral eosinophilic granuloma in the liver. A larva is not Fig.37.9 Visceral eosinophilic granuloma in the liver with palisading
seen (anymore?) . H&E epithelioid cells. A larva is not seen. the same as in Figs. 35.7 and 35.8.
H&E
HELMINTHIC DISEASES
4. Kaminsky. C. A. et al. (1989). Eosinophilic migratory nodular
panniculitis (human ganthostomiasis). Med Cutan. Ibero. Lat. Am..
17.158
5. Wilder. H. B. (1950). Nematode endophthalmitis. Trans. Am. Acad
Ophthalmol. Otolaryng.. 55. 99
6. Sakano. T. et al. (1980). Visceral laNa migrans caused by Trichuris
vulvis. Arch. Dis. Child.. 55. 63
7. Brill. R. et al. (1953). Allergic granulomatosis associated with
visceral laNa migrans. Am. J. Clin. Path .. 23. 1208
8. Stout. C. (1970). Allergic granulomas of gut (to the editor). N.
Eng/. J. Med.. 282. 1324
B. CESTODIASIS
Cestodes or tapeworms have a small head (scolex with
suckers and hooks). a short neck (proliferation zone) and
the main body has a cha:n of flat bands (proglottids)
(Table 17). Tapeworms measure from a few cm up to
20m long.
Nutrition takes place by percutaneous absorption: there
is no digestive tract. Since tapeworms are hermaphroditic,
male and female genital organs are found together in the
Table 17 Cestodes. Head and proglottids of: 1 Taenia saginata;
2 Taenia solium; 3 Diphyllobothrium latum
2 3
38. TAENIASIS
Introduction
This infection with adult worms may be caused by the
beef or pork tapeworms (Taenia saginata or Taenia solium
respectively). which are the best known worm species of
this sort in man. Carriers of these two worm species in
the digestive tract are found worldwide. Millions of
people, mostly children 1.2. are carriers. Now, infection
with Taenia solium in many countries has become rare
because of systematic meat inspection.
Taeniasis is well known in Venezuela and cysticercosis
has been found frequently in autopsy material in Merida.
It must be emphasized here that infection with eggs of
Taenia solium leads to the formation of larvae (cysticerci)
in tissues. This disease. called cysticercosis (see Section
42), is much more dangerous than the presence of pork
tapeworms in the gut (taeniasis). The latter is due to
consumption of infected raw meat. Taenia saginata does
not produce cysticercosis3-5.
The intermediate hosts for Taenia saginata are cattle
and. less frequently. zebra. buffalo. reindeer and ante-
lopes. Taenia solium is found in pigs: Taenia teniforme
141
9. Churg. J. and Strauss. L. (1951). Allergic granulomatosis. allergic
angiitis and periarteritis nodosa. Am. J. Path .. 27. 277
10. Vanek. J. (1964). Granulomata of the liver. probably of allergic
origin. Acta Morph.. XIII. 411
11. Abell. M. et al. (1970). Allergic granulomatosis with massive gastric
involvement. N. Eng/. J. Med.. 282. 665
12. Liscano. T. R. de (1972). Granulomas hepaticos en autopsias con
especial referencia a los granulomas ·eosinofflicos·. Tesis doctoral.
ULA (Merida. Venezuela)
13. Salfelder. K.. Liscano. T. R. de and Mendelovici. M. de (1973).
Visceral eosinophilic granulomas. Beitr. Path .. 149. 420
posterior proglottids of mature worms. Scolex and form
of uteri allow differentiation of species.
Man is the definitive host for mature tapeworms (in
the digestive tract) of the genera Taenia, Diphyllo-
bothrium, Dipylidium and Hymenolepis. Man may also
be the intermediate host for Taenia solium. Transmission
occurs by consumption of meat (Taenia). fish (Diphyllo-
bothrium), swallowed insects (Dipylidium) and. directly,
via eggs from man to man (Hymenolepis).
Cysticercosis and echinococcosis are diseases caused
by the larvae of tapeworms. In these cases. transmission
occurs by ingestion of eggs.
Damage to man by mature tapeworms is minimal. and
never directly fatal. The possible toxicity of these worms
is difficult to ascertain. I n contrast. the larvae of tape-
worms may lead to serious disease and cause death.
Certain infections will not be discussed in this atlas.
These are:
1. Rare infections in man by the Cestodes larvae of:
Taenia multiceps (coenurosis) which affect CNS,
subcutis and eyes.
Mesocestoides spp. with lesions in subcutis and
musculature.
Spirometra spp. (sparganosis) in subcutis, and
Sparganum proliferum with lesions of numerous
larvae in subcutis and viscera.
2. The rare infections reported only in certain countries
in South America by:
Echinococcus oligarthus,
Echinococcus vogeli and
Echinococcus patagonicus.
occurs only in rats (Fig. 38.1).
Clinically. people in contact with raw meat are liable
to get tapeworm infection. These worms seldom produce
serious clinical symptoms in man. mostly general symp-
toms of the digestive tract and loss of appetite or weight .7.
Clinical diagnosis: there may be a slight blood eosino-
philia. Eggs of Taenia are found only occasionally in
stools. For diagnosis, yellow-white tapeworm segments
or proglottids must be looked for in stools. They may also
occur spontaneously in the anal region.
The parasite
The best known tapeworms in man are Taenia saginata.
or beef, and Taenia solium, or pork tapeworm. They are
flat. segmented worms which reach. in case of T. saginata.
6-10 m and. in case of T. solium, 3-4 m in length.
.The head (scolex) is small, measuring only 1-2 mm
With 4 suckers and. In the pork tapeworm. two circles of
hooks. The segments or proglottids measure up to 20 mm
and are larger in the beef tapeworm. In the gravid
142 HELMINTHIC DISEASES

Fig. 38.1 Head of Taenia teniforme,

tapeworm of the rat. H&E

Fig.38.2 Head of Taenia saginata. H&E Fig . 38.3 Proglottid of Taenia saginata. H&E

Fig.38.4 Head of Taenia so/ium. H&E Fig.38.5 Proglottid of Taenia so/ium at high power. H&E
HELMINTHIC DISEASES
proglottids, the number of uterine branches is higher in
T. saginata than in T. solium 8 (Figs. 38.2-38.5).
In the intermediate host - and this may happen in man
too (see Cysticercosis, Section 42) - eggs containing
larvae (38 x 32 J-lm) are ingested B They are released into
the gastrointestinal tract. penetrate the wall of the small
intestine, reach the main circulation via venous blood-
stream, liver, heart and lung and are carried into almost
all organs, but mainly into the skeletal musculature. In
the tissues, the cysticercus stage of the larvae (sexless
juvenile form) develops after 2-4 months and reaches a
size of up to 10 mm in diameter. The cysticerci in tissues
of the intermediate host show as white nodules and
the meat appears measled. Under the microscope, a
connective tissue capsule surrounds the cysticercus ves-
icle with liquid which contains the inverted scolex.
The larval stage of Taenia saginata (cysticercus bovis)
develops very rarely in the intermediate host while the
cysticercus cellulosae of Taenia solium is a common
finding.
Pathogenesis
If raw infected meat. containing cysticerci, is ingested,
the gastric juice dissolves the capsule and the scolex is
everted into the lumen of the small intestine. Here, the
parasite anchors itself in the superior part of the small
bowel with the help of its suckers and/or hooks. Directly
behind the scolex, the development of a chain of proglot-
tids begins, reaching, within 3-4 months, the full length
of the mature worms (6-10 m in Taenia saginata and 3-
4 m in Taenia solium). The mature tapeworms may remain
live in the human gut for many years.
39. DIPHYLLOBOTHRIASIS
Introduction
This worm disease, also called fish tapeworm infection,
is of relatively minor importance since it may be avoided
by changing eating habits. Infections of the fresh water
tapeworm (D. latum) are found in certain regions of river
systems and lakes in Europe, the Near and Far East and
in North America. The salt water tapeworm (D. pacificum)
occurs on the coasts of South America, above all in the
north of Peru. Fishermen and people eating uncooked
fish, like eskimos, are carriers of mature fish tapeworms 1 .
Infections of this kind are not known in Venezuela.
Man is the definitive and principal host. but others
include dogs, cats, foxes and other fish-eating domestic
and wild animals as well as seals. The first intermediate
hosts are crustaceans; the second intermediate hosts are
carp and carnivorous fish.
Carriers of fish tapeworms may have slight disorders
of the gastrointestinal tract. as in taeniasis. Since fish
tapeworms take up vitamin B12 , an anaemia of the perni-
cious type may be observed, especially in eskimos. A
microcytic hypochromic anaemia has also been noted 2.3 .
Clinical diagnosis is made by detecting characteristic
eggs in the stools.
The parasite
The broad or fish tapeworm Diphyllobothrium la tum ,
found in fresh water, and Diphyllobothrium pacificum 4 in
salt water are the principal worms of this sort in man.
They may become 20 m long and are the largest tape-
worms (Fig. 39.1). The small scolex measures 2-3mm
143
Pathology
Both species of Taenia are found in the small intestine of
man. They do not invade tissues and the intestinal mucosa
remains intact although it is sometimes said to show
slight inflammation.
Quite a few cases of intestinal obstruction, perforation
or appendicitis have been reported 6. Since hundreds of
thousands of eggs may be produced and shed, infection
from man to man may lead to cysticercosis.
References
1. Hornbostel. H. (1959). Bandwurmprobleme in Neuer Sieht. Ferdi-
nand Enke, Stuttgart
2. Beier. A. (1983). Sozialmedizinische Aspekte der Bandwurmbefalls
(Taenia saginata) bei turkischen Mitburgern in Berlin (West). Bun-
desgesundheitsblatt. 26, 1 68
3. Rees, G. (1967). Pathogenesis of adult cestodes. Helminthology
Abstr.. 36. 1
4. Abudladze. K. E. (1970). Taeniata of Animals and Man and Diseases
Caused by Them. Israel program for scientific translations: Jerusalem
5. Pawlowski. Z. and Schultz. M. G. (1972). Taeniasis and cysticercosis
(Taenia saginata). Adv. Parasitol., 10. 269
6. Upton. A. C. (1950). Taenial proglottids in the appendix: Possible
association with appendicitis. Am. J. Clin. Path .. 20, 1117
7. Hurst. D. M. and Robb-Smith. A. H. J. (1942). Fatal tapeworm
enteritis. Guys Hasp. Rep .. 91. 58
8. Mehlhorn. H. et a/. (1981). On the nature of proglottids in cestodes.
Z. Parasitenkd.. 65, 343
9. Siais. J. (1973). Functional morphology of cestodes larvae. Adv.
Parasit.. 11. 395
across and is spatula-shaped with two sucker-like struc-
tures (Fig. 39.2). The mature segments (proglottids) are
10-15 mm broad and 3-5 mm long. In mature proglottids,
a small rosette-shaped uterus is found. Eggs reach
70 x 50 J-lm in diameter, have a smooth surface and have
at one end, an operculum and, at the other, a small knob
(Fig. 39.3). Those of Diphyllobothrium pacificum are
somewhat smaller.
The first intermediate hosts are small crustaceans, e.g.
the genus Cyclops, which eat the eggs and produce ciliate
larvae with hooks inside of them. The crustaceans are
eaten by the second intermediate host (carp species or
carnivorous fishes) and the larvae of the tapeworms reach
the muscles of these fishes.
Pathogenesis
Man and other definitive hosts (for instance dogs, cats,
foxes and other fish-eating animals) become infected by
consuming uncooked fish which may contain numerous
larvae.
Pathology
Fish or broad tapeworms inhabit the small intestine. They
do not invade tissues.
Rarely, related species of tapeworms fail to become
sexually mature in man (plerocercoids or spargana) and
migrate, as in the second intermediate host. into the
abdominal cavity and musculature where they may pro-
duce sparganosis (Figs. 39.4 and 39.5). Lesions of this
kind consist of clusters of parasites surrounded by granu-
144 HELMINTHIC DISEASES

Fig. 39.3 Eggs of the fish tapeworm

Fig. 39.1 Diphyllobothrium tatum orfish tapeworm. entire adult worm.

expelled after treatment

Fig. 39.4 Proglottids of Spirometra sp.

Fig. 39.5 Proglottids of Spirometra sp.

Fig. 39.2 Head of Diphyllobothrium tatum with two sucker- like

structures (sucking grooves or bothria)
HELMINTHIC DISEASES
lation tissue rich in eosinophils. Sparganosis is observed
in the USN, the former USSR, the Far East and South
East Asia.
References
1. Rausch. R. L. et al. (1967). Helminths in Eskimos in Western Alaska.
with particular reference to Diphyllobothrium infection and anaemia.
Trans. R. Soc. Trap. Med Hyg.. 61, 351
40. DIPYLIDIASIS
Introduction
This dog tapeworm infection is relatively rare in man and
occurs worldwide, mostly in children 1. The mode of
transmission of these worms is of particular interest.
Tapeworms of the genus Echinococcus occur also in dogs
as definitive hosts, but. in man, only the larvae cause
disease (echinococcosis).
Dipylidiasis is noted, also, in canine and feline species.
Fleas and dog hair lice are the intermediate hosts, in
which the dog tapeworm is observed in its cysticercoid
stage.
Clinically, symptoms, when present. are general and
observed only in massive infections or in especially
sensitive individuals.
Clinical diagnosis is made looking for proglottids and
eggs in the stools. The worm segments appear as struc-
tures similar to rice grains; they swell in water and then
show the form of proglottids. Eggs are arranged in packets.
The parasite
Dipylidium caninum or the dog tapeworm is also called
the cucumber tapeworm due to the shape of proglottids
fou nd in faeces.
Adult worms are 15-50 cm long and 2-4 mm wide. The
scolex is 0.5 mm broad with 4 suckers and 3-7 small
rows of hooks on a retractable rostellum. The elongated
41. HYMENOLEPIASIS
Introduction
Worm infection by two species of the genus Hymenolepis
may be found in man. The infection produced by Hymen-
olepis nana is the most important one and will be
discussed in the following, while infection with Hymen-
olepis diminuta will be described summarily at the end
of this Section.
The Hymenolepis nana, or dwarf tapeworm infection,
more often affects children than adults. Although this
worm disease occurs worldwide, it is more frequent in
hot countries It is said to be found in South America too.
Rates of infection run from 1% in the Southern United
States to 9% in Argentina. Cases have been described in
Venezuela 1.
In addition to man, dogs and rodents may be definitive
hosts 2 . Fleas and beetles may be intermediate hosts. Mice
are used for experimental purposes 3- 6 .
Carriers of dwarf tapeworms commonly show minimal
symptoms, as with other tapeworm infections. Only in
heavy infections do abdominal pain and other non-
specific symptoms occur. Immunosuppression favours
the development in man of this worm disease, as with
145
2. Saarni. N. (1963). Symptoms of carriers of Diphyllobothrium latum
and in non-infected controls. Acta Med Scand. 173, 147
3. Bonsdorff. B. (1977). Diphyllobothriasis in Man. Academic Press.
London
4. Lumbreras, H. et al. (1982). Single dose treatment with Praziquantel
of human cestodiasis caused by Diphyllobothrium pacificum. Tro-
penmed ParasiL 33. 5
5. Swartswelder. J. C. et al. (1964). Sparganosis in Southern United
States. Am. J. Trap. Med Hyg., 13,43
segments measure about 20 mm, are yellowish-reddish in
colour and are similar to cucumber seeds.
Individual eggs measure 25-30,um in diameter and
contain larvae with six hooks. They are excreted with
faeces in packets of 30-40 in number and are eaten by
flea larvae or dog lice (Fig. 40.1). Here the larvae hatch
out of the eggs, enter the gut of the insect. penetrate the
gut wall and reach the fat tissue. During migration in the
insect. the larva develops into a cysticercoid.
Pathogenesis
The infected fleas or lice may be ingested by the definitive
host. The scolex evaginates from the cysticercoid in the
gut and attaches itself to the gut wall where it develops
within 15-20 days into an adult worm.
Pathology
As in other cases of tapeworm infection, the worms
remain in the lumen of the digestive tract and do not
invade tissues.
References
1. Schmidt. G. D. and Roberts. L. S. (1977). Foundations of Parasit-
ology. The C. B. Mosby Company. Saint Louis
Strongyloides infection.
Clinical diagnosis is made quite easily by confirming
the presence of the characteristic eggs in the stools.
The parasite
Hymenolepis nana or dwarf tapeworm is the smallest
tapeworm living in the digestive tract of man. Commonly,
it reaches only 10-45 mm in length and 0.5-1 mm in
width. Isolated tapeworms of this sort. however, can
become quite long, although, in the presence of numerous
tapeworms, the size of each individual is small.
The scolex, measuring about 0.15-05 mm, has a small
rostellum with a single row of 20-30 hooklets and four
suckers. The proglottids are wider than they are long 7.8
(Fig. 41.1).
The eggs measure 30-50,um, are oval or spherical and
almost colourless. They occur individually in the faeces
and contain a larva with six hooks. These eggs may be
eaten by insects as intermediate hosts. When the insects
are swallowed, cysticercoids of Hymenolepis nana reach
the duodenum.
146 HELMINTHIC DISEASES

Fig. 40.1 Small packet of eggs in the uterus of Dipvlidium caninum . Fig. 41.1 Hvmenolepis nana or dwarf tapeworm. H & E
H&E
HELMINTHIC DISEASES
Pathogenesis
There are two principal means of transmission of Hymen-
olepis nana: that mentioned above, via intermediate
hosts; and direct infection, by ingestion of contaminated
food or by autoinfection. Here, the larval stage (cysticer-
coids) may develop from the eggs in the small intestine
of the definitive host. After 2-4 weeks, tapeworms may
develop from the cysticercoids.
Pathology
Dwarf tapeworms inhabit the human small intestine.
Occasionally, cysticercoids may be found inside villi of
the mucosa.
Hymenolepis diminuta, or rat tapeworm, is a cosmo-
politan parasite. Numerous cases of human infections
are observed, preferentially in children. The scolex does
not have hooklets. The eggs measure 65-75 pm in dia-
meter. Sexually mature rat tapeworms reach up to
90 cm in length. Transmission occurs always and
exclusively through intermediate hosts (insects) which
are swallowed.
42. CYSTICERCOSIS
Introduction
This disease, due to larvae (cysticerci) of Taenia solium
or the pork tapeworm, is very important, while cysticerci
bovis, due to larvae of Taenia saginata or the beef
tapeworm, occur very rarely in man 1. I n cysticercosis,
man is the accidental intermediate host after consumption
of the tapeworm eggs. The cysticerci are located in
internal organs. causing serious and dangerous disease;
50000 deaths are said to occu r each year due to
cysticercosis. Only in a small percentage of cases are
adult pork tapeworms observed in the digestive tract of
man (taeniasis solium, see Section 38) simultaneously
with cysticercosis
Cysticercosis occurs mainly in Central and South
America, Africa, I nd ia 2 and the former U SS R. It is well
known in Venezuela. In Merida, numerous cases have
been observed in biopsy and autopsy material 3
Pigs are also intermediate hosts. In these animals,
cysticerci are found preferentially in the tongue, larynx,
diaphragm, and muscles of the back and thigh, as well
as in the heart and peritoneum. The parasite is said
to occur in the liver, lungs and brain. Experimentally,
cysticercosis may be induced in rhesus monkeys 4
Clinically, CNS symptoms are the most frequent and
important in man. Often, epileptiform convulsions occur,
or disorders, apparently due to tumour-like lesions, pre-
vail. Neurological and mental symptoms depend on the
location of the brain lesions. The direct cause of death
is usually internal hydrocephalus. Involvement of the
musculature is often symptomless, but rheumatic pain
may occur Ocular cysticercosis may lead to blindness.
Clinical diagnosis is possible by confirming the pres-
ence of calcified cysticerci with X-ray. Immunological
methods and computed tomography are usefuI 5- 8 , but
there are only group-specific antigens available. Lately,
MR (magnetic resonance) has been applied successfully
in neurocysticercosis 9- 11 .
147
References
1. Soto Umbarri, R. and Torazon, S. S. de (1988). Efecto terapeutico
de Praziquantel sobre Hymenolepis nana. Kasmera, 16, 51
2. Hauff, P. and Arnold, W. (1990). Spontaneous Hymenolepis nana
infection in a breeding colony of nude mice. Z. Versuchtstierkd.. 33,
133
3. Kilkinov, G. T. (1967). Unusual cases of Hymenolepis nana localiz-
ation in experimental Hymenolepsis infection. Trap. Dis. Bull, 64,
994
4. Novak, M. and Nombrado, S (1988). Mast cell responses to
Hymenolepis microstoma infection in mice. J Parasito/., 74, 81
5. Novak, M. et a/. (1990). Effects of cyclophosphamide and dexa-
methasone on mast cell population in Hymenolepis microstoma-
infected mice. Parasitology, 100. 337
6. Van der Vors!, E. et al. (1990). Hymenolepis diminuta: intestinal mast
cells and eosinophil response of the mouse to infection. Ann. Soc.
Belg. Med. Trap, 70, 113
7. Becker. B. et a/. (1980). Scanning and transmission electron micro-
scope studies on the efficacy of praziquantel on Hymenolepis nana
(Cestoda) in vitro. Z. Parsitenkd., 61, 121
8. Becker. B. et a/. (1980). Ultrastructural investigations on the effect
of praziquantel on the tegument of five species of Cestodes. Z.
Parasitenkd., 64, 257
The parasite
Larvae of the pork tapeworm (Taenia solium) represent
the sexless juvenile forms and are called cysticerci,
Cysticercus cellulosae or Taenia solium cysticercus. Their
structure is the same in tissues of man and pig.
On average, they measure 1 cm in diameter and consist
of a vesicle, which contains liquid, and a connective
tissue capsule surrounding the vesicle. The larva swims
in the liquid and presents an inverted scolex with hooks.
Cysticercus bovis does not have hooks (Fig. 42.1).
Pathogenesis
Eggs of Taenia solium are ingested by man with contami-
nated food, often salad vegetables. They transform in the
lumen of the digestive tract into larvae, penetrate the
intestinal wall and reach the internal organs via the
bloodstream. They remain in the tissues and grow up to
a certain size for 2-4 months. They then remain infectious
in the tissues for 1-2 years. Theoretically, when antiperi-
stalsis occurs in carriers of Taenia solium, so-called
retroinfection may take place and the proglottids will
shed eggs into the stomach making development of
cysticercosis possible. Intrauterine infection of a fetus
may occur from the third month of pregnancy onwards.
In the other intermediate host. the pig, pathogenesis is
the same when eggs of Taenia solium are ingested The
pork meat then appears measly with white nodules. When
this meat is eaten raw, adult tapeworms will develop in
the human gut (taeniasis solium, Section 38).
Pathology
In man, there isa kind of tropism regarding involvement
of organs. Cysticerci are located mainly in the central
148
nervous system 12- 14 (Figs. 42.2-42.5), the skeletal muscu-
lature (Fig 42.6) and subcutis, in descending order of
frequency.
Occasionally, the eyes may be involved, and, rarely,
cysticerci may be found in other organs, such as the
heart (Fig. 42.7), peritoneum, tongue 15 , li ps 16 and orbital
muscles 17
In the brai n, exceptionally, cysticercus racemosus may
be observed; this has the appearance of large thin-walled
cysticercus cysts, up to 10 cm in diameter, arranged in
clusters, like bunches of grapes.
Histologically, when the inverted scolex is cut appropri-
ately, hooks may be seen clearly in the sections (Figs.
42.8-42.10). After the death of the larva, a slight non-
specific inflammatory reaction appears and, later, calci-
fication takes place. Sometimes, calcified deposits which
mimic spherical structures, i.e. eggs, are observed. How-
ever, eggs are not formed by larvae. Concomitant infec-
tions of cysticerci are rare 18 Occasionally, a foreign body
reaction may be observed (Fig. 42.11).
References
1. Froyd. G. (1965). The incidence of Cysticercus bovis. Bul/. Ofr Int.
Epiz., 63, 311
2. Venkataraman, S. et al. (1990). Cysticercal meningoencephalitis.
Clinical presentation and autopsy findings. J. Assoc. Physicians
India, 38, 763
3. Rada Fangher. R. G. (1964). Neurocvsticercosis. Universidad de
los Andes. Facultad de Medicina, Centro Neurol6gico, Merida/
Venezuela
43. ECHINOCOCCOSIS
Introduction
This disease is produced by two main tapeworm species
and may be called echinococcosis, hydatidosis, hydatid
worm infection or alveolar echinococcosis 1 . Man may
become infected as an intermediate host. The tapeworm
species are A Echinococcus granulosus and B Echino-
coccus multilocularis; each produces a disease, with
different features, by ingestion of worm eggs. Adult tape-
worms of the genus Echinococcus, however, occur
only in animals, mainly dogs and foxes, as definitive
hosts. Echinococcosis is the most dangerous tapeworm
infection in man. It is caused by the larvae of these worms
producing cyst-like or tumour-like lesions.
A is more frequent than B. It occurs in parts of Europe,
South America, mostly the south, Africa and South
Australia. Single autochthonous infections have also been
noted in Venezuela 23 B is endemic in parts of the northern
hemisphere, Europe, the former USSR, USA and Canada 4- B
In A the definitive hosts, with adult worms, are dogs,
cats and canine species. B occurs only in wild animals.
The intermediate hosts, with lesions due to larvae, are, in
addition to man, sheep, camels, domestic animals and
small rodents 10 Experimentally mice may be used 11 .12
Clinically, symptoms develop according to the location
of lesions. In liver and lungs, the most affected organs,
lesions may remain asymptomatic for a long time. They
grow and increase in size slowly. As they enlarge, they
cause atrophy of the surrounding tissues by compression
and may be painful. Care must be taken when removing
lesions surgically because the parasitic elements within
the cyst content may be disseminated after the rupture of
the cystic wall, producing local or disseminated meta-
HELMINTHIC DISEASES
4. Saleque. A. et al. (1988). Induced Taenia solium cysticercosis in
rhesus monkeys (Macaca mulatta): a clinico-pathological study.
Ann. Trop. Med. Parasitol" 82, 103
5. Proctor, E. M. (1966). The serological diagnosis of cysticercosis.
Ann. Trap. Med. Parasitol" 60, 146
6. Gottstein, B. et a/. (1986). Antigenanalyse von Taenia solium und
spezifische Immundiagnose der Zystizerkose beim Menschen. 12.
Tg. Dtsch. Ges. Parasit. Referat Nr, 32, Wien
7. Hoffman, P. et al. (1990). Atteinte isolee du systeme nerveux
central au cours d'une cysticercose. Etude anatomo-clinique d'une
observation. Ann. Pathol, 10, 122
8. Dhamija. R. M. et a/. (1990). Computed tomographic spectrum of
neurocysticercosis. J. Assoc. Physicians India. 38, 566
9. Jena, A. et al. (1988). Cysticercosis of the brain shown by magnetic
resonance imaging. Clin. Radial" 39, 542
10. Zee, C. S. et al. (1988). MR imaging of neurocysticercosis. J.
Comput. Assist. Tomogr" 12, 927
11. lotz, J. eta/. (1988). Neurocysticercosis: correlative pathomorphol-
ogy and MR imaging. NeuroradiologV, 30. 35
12. Alarcon Egas, F. et a/. (1988). Neurocisticercosis: a review of 65
patients. Arch. Neurobiol Madr., 51, 252
13. Esberg. G. and Reske-Nieksen. E. (1988). Sudden death from
cerebral cysticercosis Scand. J. Infect. Dis, 20, 679
14. McKelvie, P. A. and Goldsmid, J. M. (1988). Childhood central
nervous system cysticercosis in Australia. Med. J. Aust., 149, 42
15. Rao, P. L. et a/. (1990). Cysticercosis of the tongue. Int. J. Pediatr.
Otorhinolarvngol" 20, 159
16. Fazakerley, M. W. and Woolgar. J. A. (1991). Cysticercosis cellulo-
sae. An unusual cause of a labial swelling. Br. Dent. J.. 170. 105
17. Diloreto, D. A. et al. (1990). Infestation of extraocular muscle by
Cysticercus cellulosae. Br J. Ophthalmol, 74, 751
18. Walus, M. A. and Young, E. J. (1990). Concomitant neurocy-
sticercosis and brucellosis. Am. J. Clin. Pathol.. 94. 790
stases by lymphogenous or haematogenous spread. Con-
sequently, new hydatid cysts (secondary hydatidosis) 13
or tumour-like lesions may be formed. Furthermore,
fatal anaphylactic shock may occur as a result of the pro-
teinogenous liquid spilled into the body cavity during
surgical removal of the cyst.
Clinical diagnosis: cavitary lesions may be seen by
tomography and sonography, and calcified cysts by X-
ray. Scolices and isolated hooks may be confirmed by
cytology and histology for instance in sputum after rupture
of cysts into the airways. In lesions with multiple cysts
in B, caused by E. multilocularis, scolices are mostly
absent. With immunological methods, cross reaction with
Taenia cysticercus must be taken into consideration.
Frequently, the most difficult differential diagnosis to
make is with malignant tumour.
The parasite
This disease is caused by larvae of the two main Echino-
coccus species found in man (see Pathology below);
A Echinococcus granulosus, Echinococcus cysticus or
Echinococcus hydatidicus is also called hydatid worm
or dog tapeworm (Figs. 43.1 and 43.2).
B Echinococcus (Alveococcus) multilocularis or Echin-
ococcus alveolaris is also called fox tapeworm.
The mature worms are never seen in man. They reach
< 1 cm long in the small intestine of the definitive hosts
(A is a little longer than B). There are only 3-4 proglottids.
Occasionally, single proglottids are shed, containing num-
erous eggs; the segments are then replaced.
HELMINTHIC DISEASES 149

Fig. 42.1 Cysticercus bovis. H&E Fig. 42.2 Cysticercus ce/lu/osae visible in the surface of the human
brain

Fig.42.3 Cysticercus ce/lu/osae at the cut surface of the human brain Fig. 42.4 Cysticercosis with marked deformation at the cut surface of
the human brain

Fig. 42.5 Cysticercus ce/lu/osae obstructing the Aquaeductus Sylvii

Fig.42.6 Numerous Cysticercus cellulosae in the skeletal musculature

of both forearms
150 HELMINTHIC DISEASES

Fig. 42.7 Small subendocardial Cysticercus ce/lu/osae in the left

ventricle

Fig.42.8 Inverted scolex of Cysticercus ce/lu/osae with hooks in the Fig. 42.9 High magnification of Fig. 42.8 with the hooks clearly
centre. H&E visible. H&E

,I

Fig. 4.10 The hooks of scolex of Cysticercus ce/lu/osae in another Fig.42.11

. ,
•
Foreign body reaction around a cysticercus in the meninges.
projection H&E
HELMINTHIC DISEASES
Pathogenesis
This is similar in A and B. The eggs of Echinococcus
worms are ingested by man and reach the liver, lungs and
other organs after penetrating the wall of the small
intestine. Here, they grow, in a kind of larval stage, very
slowly over the course of years never reaching maturity,
i.e. formation of adult worms. Instead, they form solitary
cystic lesions in A and tumour-like lesions in B. In the
latter, they remain a long time in the liver and eventually
disseminate from this organ to others in a tumour-like
manner.
Pathology
During infection with A, solitary unilocular hydatid cysts
may be found in liver (Figs. 43.3-43.8), spleen, lungs,
eN S14-16, bones 17.18 (Figs. 43.9-43.11 ) and other organs 19
(Figs. 43.12 and 43.13). From the liver, there may be
extension to thoracic organs 20 On average they measure
5 cm in diameter and are filled with fluid. Frequently, in
the liver they reach larger dimensions up to more than
20 cm. The cyst is surrounded by a connective tissue
capsule formed by the host. The internal surface is lined
by a germinal layer with daughter cysts or brood capsules
showing scolices. In the fluid of the cysts, entire scolices
may be found (Fig. 43.14).
Lesions due to infection with Echinococcus multilocu-
laris (B) are quite different from those due to Echinoc-
occus granulosus (A). They are found mainly in the liver
and consist of a focal tumorous lesion with numerous
small vesicles filled with a gelatinous substance. Scolices
are not always present since lesions may be sterile. Often,
cystic cavities can no longer be recognized, but a fibrous
network prevails with partly tubular or rope-like structure.
Further, areas with marked necrosis, forming cavities,
calcifications and haemorrhages, may be observed.
Grossly, these lesions very much resemble malignant
tumours. Secondary metastatic lesions may be found in
lymph nodes, lungs and other organs. In laboratory
animals, metastases have been observed, apparently due
to detached cells which have been disseminated by
lymphogenous or haematogenous spread.
References
1. Miguel. J. P. and Bresson-Hadni, S. (1989). Alveolar echino-
coccosis of the liver. J. Hepatol. 8, 373
C. TREMATODIASIS
Trematodes or flukes are flat or tongue-shaped worms
with an oral orifice and digestive tract and without
segmentation. Many species possess suckers. All are
hermaphrodites, with the exception of the schistosomes.
In the definitive hosts, they occur as mature worms; larval
development occurs in one or two intermediate hosts,
mainly snails or aquatic animals.
Adult trematode worms in man, as the definitive host.
44. BLOOD FLUKE INFECTION
Introduction
Infection by blood trematodes or blood flukes is also
called schistosomiasis, bilharziasis or 'water snail fever'
It is an important disease because 200-300 million people
in warm countries, mostly children and young people, are
infected; also, in non-tropical regions, an increasing
151
2. Salfelder, K. et a/. (1967). Caso de equinococcosis aut6ctona en
Venezuela. Tribuna Med Venezuela, 204, 1
3. Bont de. F. P. and Sauerteig. E. (1970). A prop6sito de un caso de
equinococcosis aut6ctona del Estado BarinaslVenezuela. Rev. Col
Med. Edo. Merida, XI. 75
4. Blood, B. D. and Leilijveld, J. L. (1969). Studies on sylvatic
echinococcosis in Southern South America. Z. Tropenmed. Parasit..
20, 475
5. Lukashenko, N. P. (1971). Problems of epidemiology and prophy-
laxis of alveococcosis (Multilocular echinococcosis): a general
review - with particular reference to the USSR. Int. J. Parasit.. 1,
125
6. Williams, J. F. et a/. (1971). Current prevalence and distribution of
hydatidosis with special reference to the Americas. Am. J Trop.
Med. HVg.. 20, 224
7. Hagedorn, H. J. (1982). Zystische Echinococcose. Dtsch. Arzre-
blatt. 44. 34
8. Chi, P. et a/. (1990). Cystic echinococcosis in the Xinjiang/Uygur
Autonomous Region, People's Republic of China. I. Demographic
and epidemiologic data. Trop Med. Parasit.. 41, 157
9. Auer, H. et a/. (1990). First report on the occurrence of human
cases of alveolar echinococcosis in the Northeast of Austria. Trop.
Med. Parasir., 41, 149
10. Gusbi, A. M. et a/. (1990). EchinococcosIs in Libya. IV. Prevalence
of hydatidosis (Echinococcous granulosus) in goats. cattle and
camels. Ann. Trop. Med Parasitol.. 84, 477
11. Eckert, J. et al. (1983). Proliferation and metastases formation of
larval Echinococcus multilocularis. I. Animal model. macroscopical
and microscopical findings. Z. Parasitenkd, 69, 737
12. Richards. K. S. et a/. (1988). Echinococcus granulosus: the effects
of praziquantel. in vivo and in vitro, on the ultrastructure of equine
strain murine cysts. ParasitologV, 96, 323
13. Felice, C. et a/. (1990). A new therapeutic approach for hydatid
liver cysts. Aspiration and alcohol injection under sonographic
guidance. Gastroenterologv. 98, 1366
14. Richards, K. S. and Morris, D. L. (1990). Effect of albendazole on
human hydatid cysts: an ultrastructural study. HPB Surg.. 2, 105
15. Jena. A. et al. (1991). Primary spinal echinococcosis causing
paraplegia: case report with MR and pathologic correlation. AJNR
Am. J. Neuroradiol, 12, 560
16. Altinors, N. et al. (1991). CT findings and surgical treatment of
double intracranial echinococcal cysts. Infection. 19, 110
17. Akyildiz, A. N. et al. (1991). Hydatid cyst of the pterygopalatine
fossa. J. Oral Maxillofac. Surg.. 49, 87
18. Fyfe, B. et al. (1990) Intraosseous echinococcosis a rare manifes-
tation of echinococcal disease. South Med. J, 83, 66
19. Gilevich, Miu eta/. (1990). Clinico-morphological bases of selection
of the methods of treatment of echinococcosis of the abdominal
organs and retroperitoneal space. Khirurgiia Mask.. 11, 116
20. Pinna. A. D. et al. (1990). Thoracic extension of hydatid cysts of
the liver. Surg Gvnecol Obstet.. 170, 233
are found in blood, lungs, liver and intestine. Only
schistosomes cause damage in man by their eggs. The
medicinal blood fluke, Hirudo medicinalis, used for bleed-
ing, is segmented and is not a pathogen.
Only three of the fifteen medically important trematode
species occur in countries of the New World, mostly in
South America.
number of 'imported' cases is found.
From the five different species of the genus Schisto-
soma, only three are medically important. namely S.
haematobium, S. mansoni and S. japonicum. They occur
in Africa and the Near and Middle East (5. haematobium) ,
in central Africa (5. intercalatum) , in the Far East and
152 HELMINTHIC DISEASES

Fig. 43.1 Echinococcus granu/osus. Carmine Fig. 43.2 Hooks on the scolex of Echinococcus granu/osus. Carmine

Fig.43.3 Wall of a hydatid cyst in the liver. H&E Fig.43.4 Brood capsule containing several scolices of Echinococcus
granu/osus in a hydatid cyst of the liver. The thin capsule of the brood
capsule is faintly visible. H&E
HELMINTHIC DISEASES 153

Fig. 43.5 Scolex of Echinococcus granu/osus attached to the mem~

brane of the brood capsule. H &E

Fig. 43.6 Scolex of Echinococcus granu/osus in hydatid cyst of the Fig. 43.7 Scolex of Echinococcus granu/osus in hydatid cyst of the
liver. Note the hooks. H&E liver. Note the hooks cut horizontally. Compare with Fig. 43.5. H&E

Fig. 43.8 Single hook of scolex of Echinococcus granu/osus from the

contents of hydatid cyst of the liver. H&E

Fig. 43.9 Foreign body reaction with hooks of Echinococcus gran~ Fig.43.10 Same case as Fig. 43.9. Fragments of hooks in giant cells.
u/osus in a giant cell from a lesion in the ribs. H&E H&E
154 HELMINTHIC DISEASES

Fig. 43.11 Same case as Fig. 43.8. Crown of hooks Fig.43.12 Deformed scolex of Echinococcus granulosus with faintly
in the contents of a cyst. H&E visible hooks in the peritoneal exudate. A case with involvement of
peritoneum. H&E

Fig. 43.13 Necrobiotic scolex of Echinococcus granulosus with fa intly Fig. 43.14 Numerous scolices of Echinococcus granulosus in
visible hook. Same case as Fig. 43.12. H&E unstained smear of the fluid in a cyst. They appear bluish because
photography was done with a filter
HELMINTHIC DISEASES
South East Asia (S. japonicum) , in Laos and Cambodia
(S. mekonpi) and in Africa and South America (S.
mansoni) 1- . Areas endemic for schistosomiasis are known
in the central regions of Venezuela
Definitive hosts, in addition to man, and reservoir hosts
are, depending on parasite species, monkeys, rodents and
several species of domestic animals 5 . Intermediate hosts
are water snails. For experimental studies, mice. hamsters
and rats may be used 6- 11 .
Clinically, an allergic dermatitis may be observed (cer-
carial dermatitis). Four to seven weeks after infection,
clinical manifestations caused by worms and worm eggs
may be noted. Many cases, however, remain asympto-
matic for a long time. Symptoms appear according to the
location of the lesions: in the digestive tract (sometimes
with dysenteric-like bloody diarrhoea), in the liver, or in
the urogenital region. Exceptionally, other organs may be
involved. In chronic infections, carcinoma of the bladder
may be observed.
Clinical diagnosis is made by confirmation of the
characteristic worm eggs in stools or urine. Biopsy of the
rectal mucosa may be helpful 1213 , and, serologically,
different antigens exist for diagnosis of acute and chronic
infections 14
The parasite
The five species, Schistosoma haematobium, S. interca/a-
tum, S. japonicum, S. mansoni and S. mekongi. occur in
different geographical areas (see above). S. mekongi
is very similar to S. japonicum. Recently, Schistosoma
curassoni has been found to be an important species in
Senegal 15 .
Adult male and female worms of the genus Schistosoma
measure from 6-24 mm in length with slight variations
according to the species. Females are somewhat longer
and thinner. I n the blood vessels of the definitive host.
female worms are found within a longitudinal (gynae-
cophoric) canal of the male worm. The latter has a similar
appearance to a rowing boat. Therefore they are also
named 'paired flukes' (Fig. 44.1).
The worm eggs have particular characteristic features
and sizes which allow differentiation of the five species
(Fig. 44.2).
S. haematobium - elliptical. terminal spine, 150 x 55 pm
S. interca/atum - elliptical. slimmer than S. haematobium,
terminal spine, 140 x 150 pm
S. japonicum - oval. small lateral kob, 90 x 55 pm
S. mansoni - elliptical, lateral spine, 150 x 60 pm
S. mekongi - spherical, lateral knob, 40 x 45 pm
Development of the different Schistosoma species IS
similar. Eggs are excreted in stools or urine and reach the
water. There, a larva with cilia, called a miracidium,
hatches out from the egg and penetrates into a snail.
Here. the larvae become infectious, transform into fork-
tailed cercaria (Fig. 44.3) and reproduce copiously. After
being released into water again, they can infect a definitive
host.
Pathogenesis
There is no transmission from man to man or animal or
man. Infection takes place only in water.
The fork-tailed cercaria penetrates through the intact
skin of the definitive host. quickly loosing its tail. Through
lymph and bloodstream, it reaches the mesenteric, liver
and bladder veins (only S. haematobium) where the
flukes become mature. Here, copulation of male and
female worms takes place and production of eggs begins.
The eggs pass through the intestinal and bladder walls
155
into the lumina of these organs and the developmental
cycle begins again outside of the human body.
The eggs produce tissue lesions in the intestinal and
bladder wall. and they may be disseminated, haematogen-
ously, to almost all organs, causing further tissue alter-
ations. Damage to human tissue caused by adult Schisto-
soma worms is of minor importance.
Pathology
Skin, intestine, liver. spleen, the urogenital tract. lungs,
CNS and other organs (exceptionally) may be involved.
Grossly, cercarial dermatitis (Fig. 444) may manifest
itself with red areas and transient papulomatous skin
lesions.
Intestinal schistosomiasis, caused by S. mansoni, S.
japonicum, S. mekongi and S. interca/atum, shows mani-
festations in the ileocaecal region and the large bowel.
In the intestinal mucosa and peritoneum, nodular tuber-
cle-like lesions may be present (Fig. 44.5). A marked
acute or chronic colitis, with haemorrhages, ulceration
and polypoid lesions, may be observed, as well as appen-
dicitis 16
Hepato- and splenomegaly, as well as hepatitis.
pipe stem fibrosis of the liver and portal hypertension,
due to portal vein obstruction may occur. These alterations
may cause fatal oesophageal bleeding from varices pro-
duced by the Schistosoma species mentioned above, with
the exception of Schistosoma interca/atum 1718 Fig. 44.6
shows liver granulomas due to Schistosoma infection.
Urogenital schistosomiasis, caused only by S haema-
tobium, may show acute and chronic cystitis,
pyelonephritis, urolithiasis and hydronephrosis192o Fur-
thermore, female (Fig. 44.7) and male genital organs 21
may be involved. In severe and chronic infections, cancer
of the bladder may develop. Squamous cell carcinomas
are more common than transitional carcinomas (Figs.
44.8 and 44.9).
I n the lungs, obstructive arteritis may lead to cor
pulmonale (Figs. 44.10 and 44.11).
In the central nervous system 22 - 24 and other
organs, lesions caused by blood flukes are (Figs. 44.12-
44.14) rare and not characteristic
Histologically, Schistosoma eggs produce eosinophilic
granulomas in the intestinal wall, liver, urogenital tract
and elsewhere. These granulomas later undergo fibrosis.
The eggs disintegrate and may be calcified. Granulomas
of this type may be confused with those due to larva
migrans, see Section 37 Surrounding the eggs, the
Hoeppli-Splendore phenomenon may be observed 25 .
Pipe stem fibrosis in the liver is rather typical and occurs
without active schistosomiasis lesions.
When there is pulmonary involvement. the worm eggs
produce granulomas situated in the vicinity and adventitia
of pulmonary arteries which, consequently lead to their
obliteration, followed by pulmonary hypertension and
hypertrophy of the right heart ventricle (cor pulmonale).
The glomerulonephritis found in patients with schisto-
somiasis is of an immunological type (without the pres-
ence of a causal agent) 26-28
References
1. Doumenge. J. P. et at. (1987). Atlas de la Repartition Mondiale des
Schistosomiases. CEGET-CNRS/OMS-WHO. Presses Universit-
aires de Bordeaux
2. Butterworth. A. E. et al. (1988). Longitudinal studies on human
schistosomiasis. Phi/os. Trans. R. Soc. Land. BioI.. 321, 495
3. Vargas. M. eta/. (1990). Schistosomiasis mansoni in the Dominican
Republic; prevalence and intensity in various urban and rural
communities. 1982-1987. Trap. Med. Parasirol.. 41. 415
4. Hatz. C. et at. (1990). Ultrasound scanning for detecting morbidity
156 HELMINTHIC DISEASES

Fig. 44.1 Female worm of Schistosoma mansoni within a longitudinal Fig. 44.3 Fork-tailed cercaria of Schistosoma mansoni. Carmine
(gynaecophoric) canal of the male. Carmine

a. b.

Fig. 44.2 Eggs of the genus Schistosoma: c. d.

a. Schistosoma haematobium (in urine) H&E;
b. Schistosoma japonicum (in faeces);
c. Schistosoma mansoni (in tissue with lateral spine) H&E;
d. Schistosoma mansoni (in tissue with lateral spine and Hoeppli-
Splendore phenomenon) H&E
HELMINTHIC DISEASES 157

Fig. 44.4 Cercarial dermatitis in a 62-year-old male patient from Fig. 44.5 Schistosoma granuloma in the submucosa of appendix.
Barinas. Venezuela H&E

Fig. 44.6 Schistosoma granulomas in the liver in different stages of

evolution with and without parasitic eggs. H &E
158 HELMINTHIC DISEASES

Fig.44.7 Schistosoma granuloma at the uterine cervix. H&E Fig.44.8 Squamous cell carcinoma of the bladder with Schistosoma
eggs. H&E

Fig. 44.9 Numerous deformed eggs of Schistosoma haematobium in Fig. 44.10 Schistosoma granuloma in the lung near the pulmonary
the case of Fig . 44.8. H&E artery. A case with cor pulmonale. H&E
HELMINTHIC DISEASES 159

Fig. 44.11 Pulmonary Schistosoma granuloma with parasitic egg Fig. 44.12 Schistosoma meningo-myelitis with granuloma. Small
clearly visible. Same case as Fig. 44.10. H&E deformed parasitic egg faintly visible in the centre of granuloma. H &E

Fig.44.13 Same case as Fig. 44.12 at higher power with Schistosoma Fig.44.14 Same case as Figs. 44.12 and 44.13 . In two Schistosoma
egg clearly visible. H&E eggs miracidium structures are seen. The latter may be confused with
multinuclear tissue giant cells. H&E
160
due to Schistosoma haematobium and its resolution following
treatment with different doses of praziquantel. Trans. R. Soc. Trap.
Med. Hyg., 84, 84
5. Obwolo, M. J. and Rogers, S. E. (1988). Schistosomal lesions in
the bovine uterus. J. Compo Pathol., 98, 501
6. Vignali, D. A. et al. (1989). Histological examination of the cellular
reaction around schistosomula of Schistosoma mansoni in the lungs
of sublethally irradiated and unirradiated immune and control rats.
Parasitology, 98, 57
7. Cheever, A. W. and Deb, S. (1989). Persistence of hepatic fibrosis
and tissue eggs following treatment of Schistosoma japonicum
infected mice. Am. J. Trap. Med. Hyg., 40, 620
8. Andrade, Z. A. and De Azevedo, T. M. (1987). A contribution to
the study of acute schistosomiasis (an experimental trial). Mem.
Inst. Owaldo Cruz, 82, 311
9. Andrade, Z. A. (1987). Pathogenesis of pipe stem fibrosis of the
liver (experimental observation on murine schistosomiasis). Mem.
Inst. Os waldo Cruz, 82, 325
10. Melro, M. C. and Mariano, M. (1987). Extra-tissular Schistosoma
mansoni egg granulomata in the peritoneal cavity of mice. Mem.
Inst. Os waldo Cruz, 82 Suppl. 4, 245
11. He, Y. X. et al. (1989). Dermal responses of various hosts to
infection with Schistoma japonicum cercariae. Chung. Kuo. Chi., 7,
15
12. Meybehm, M. et al. (1989). Granulomatous colitis with pseudo-
polyp in schistosomiasis. Dtsch. Med. Wschr., 114, 19
13. Yasawy, M. I. et al. (1989). Comparison between stool examination,
serology and large bowel biopsy in diagnosing Schistosoma man-
soni. Trap. DOCL 19, 132
14. Boros, D. L. (1989). Immunopathology of Schistosoma mansoni
infection. C/in. Microbiol. Rev., 2, 250
15. Vercruysse, J. (1990). Schistosoma species in Senegal with special
reference to the biology, epidemiology and pathology of Schisto-
soma curassoni Brumpt 1931. Verh. K. Akad. Geneeskd. Belg.. 52,
31
16. AI-Kraida, A. et a/. (1988). Appendicitis and schistosomiasis. Br. J.
45. LUNG TREMATODE INFECTION
Introduction
Autochthonous pulmonary fluke infection, or paragoni-
miasis, pulmonary distomiasis or endemic haemoptysis,
is limited to certain geographical areas and practically
found only in people with particular nutritional habits.
There are three species of the genus Paragonimus
important for human infection:
1. P. westermani in the Far East the Philippines and
India,
2. P. africanus in the tropical countries of West Africa 1 ,
and
3. P. kellicotti in North, Central and certain countries of
South America, e.g. in Venezuela.
With their eggs, they may contribute to the contamination
of water. The definitive hosts, in addition to man, are
numerous species of domestic and fur-bearing animals 23 .
The first intermediate hosts are water snails and the
second intermediate hosts are crabs and crayfish. Each
species of Paragonimus has its specific intermediate hosts.
Experimentally, dogs and Rhesus monkeys, as well as
cats, have been used 4
Clinically, symptoms depend on the number of worms
in the lungs and the other sites, where worms may be
located eventually. Often, a chronic bronchitis with blood
in sputum is present and differential diagnosis may be
tuberculosis 5 . In China, some cases have been reported
with no eggs in the sputum, but with heavy enlargement
of the Iiver 6.
Clinical diagnosis is made by confirmation of golden-
brown operculated eggs in the often blood-stained spu-
tum and in stools. X-ray, tomography and sonography
may lead to suspicion of pulmonary parasitic disease
since the cysts may look like tumours (parasitic pseudotu-
HELMINTHIC DISEASES
Surg., 75, 58
17. Hamadto, H. A. et al. (1990). Correlation between intensity of
infection and hepatic histopathological lesions in bilharzial patients.
J. Egypt. Soc. Parasitol., 20, 147
18. Doehring-Schwerdtfeger, E. eta/. (1990) Ultrasonographical inves-
tigation of periportal fibrosis in children with Schistosoma mansoni
infection; evaluation of morbidity. Am. J. Trop. Med. Hyg., 42, 581
19. Adolphs, H.-D. et al. (1982). Manifestation der Bilharziose am
Harntrakt. Act. Ural., 13, 277
20. Laurent C. et a/. (1990). Ultrasonographic assessment of urinary
tract lesions due to Schistosoma haematobium in Nigeria after
four consecutive years of treatment with praziquantel. Trap. Med.
Parasitol.. 41, 139
21. Mikhail, N. E. et al. (1988). Schistosomal orchitis simulating
malignancy. J. Ural, 140, 147
22. Andrade, A. N. and Bastos, C. L. (1989). Cerebral schistosomiasis
mansoni. Arqu. Neuropsiquiatr.. 47, 100
23. Pitella, J. E. (1991). The relation between involvement of the central
nervous system in schistosomiasis mansoni and the clinical forms
of the parasitosis. A review. J. Trop. Med. Hyg., 94, 15
24. Selwa, L. M. et al. (1991). Spinal cord schistosomiasis: a pediatric
case mimicking intrinsic cord neoplasm. Neurology, 41, 755
25. Kephart, G. M. et a/. (1988). Localization of eosinophil basic protein
onto eggs of Schistosoma mansoni in human pathologic tissue.
Am. J. Pathol. 133, 389
26. Sobh, M. A. etal. (1988). Characterization of kidney lesions in early
schistosoma I-specific nephropathy. Nephral. Dial Transplant.. 3,
392
27. De Water, R. et al. (1988). Schistosoma mansoni: ultrastructural
localization of the circulating anodic antigen and the circulating
cathodic antigen in the mouse kidney glomerulus. Am. J. Trap.
Med. Hyg., 38, 118
28. Sobh, M. W. et al. (1991). Schistosoma haematobium-induced
glomerular disease: an experimental study in the golden hamster.
Neprhon. 57, 216
mours). In serological tests, cross-reactions with Schisto-
soma infection may occur.
The parasite
There are more than 20 species of lung trematodes and
numerous ones of the genus Paragonimus 5 . The best-
known pulmonary flukes in man are Paragonimus wester-
mani, mostly in China, P. africanus and P. ke//icotti.
The adult worms of Paragonimus measure 7-12 x
4-7 mm and are egg-shaped. They are reddish brown,
like a roasted coffee bean, have two suckers and numer-
ous prominent spines on the surface. Their lifespan in
man may be more than 20 years.
The eggs are golden-brown, measure 90 x 60.um and
have an operculum at one end. They contain 5-10 yolk
cells when immature, and, once laid, a miracidium larva
grows within.
The eggs reach the exterior mostly with the sputum. In
water, the hatched larval miracidia from the eggs penetrate
into snails (the first intermediate host). There, cercariae
with short tails and fine spines develop. They reach the
water again, where they are eaten by crayfish and crabs.
Inside these crustaceans (the second i ntermed iate hosts),
the cercaria encyst and transform into metacercariae
which are situated in certain muscles.
Pathogenesis
Man is infected by consuming raw crab or crayfish meat.
The metacercariae then reach the small intestine of the
definitive host. Metacercariae are present too in the juice
of crushed crustaceans and transmission may also take
place, exceptionally, through handling infected crus-
taceans or eating raw pork meatl 8
HELMINTHIC DISEASES 161

Fig. 45.1 Paragonimus westermani fluke in a pulmonary cyst. H&E Fig.45.2 Another large Paragonimus westermanifluke in a pulmonary
cyst. H&E

Fig. 45.3 The spines on the surface of these lung flukes are easily Fig. 45.4 Eggs of Paragonimus westerman; in the granulation tissue
recognized. H&E around the flukes in the lung. H&E
162 HELMINTHIC DISEASES

Fig. 45.5 Lung cyst in a case of paragonimiasis containing exudate Fig. 45.6 The same cyst as Fig. 45.5 with polarized light. H&E
with surrounding parasitic eggs. H&E

Figs. 45.7a and b Eggs of Paragonimus westermani in lung tissue.

H&E
HELMINTHIC DISEASES
The metacercariae in the human small intestine hatch
out of their shells as young flukes and penetrate the wall
of the duodenum. Here. migration through the diaphragm
into the thoracic cavity takes place. mostly with invasion
of the lungs.
Pathology
Although the lungs are involved chiefly. aberrant flukes
may reach extrapulmonary sites and remain there. Para-
gonimiasis lesions have been reported in the peritoneum.
omentum. skin. liver 6. spleen. pancreas. kidneys. brain 9
and spinal cord.
In the lungs. young flukes are soon surrounded and
enclosed by a fibrous wall. forming a cyst-like cavity.
where they become sexually mature over the course of
2~3 months. These cysts are situated mostly in the vicinity
of bronchi; they reach 1 ~2 cm in diameter. Several flukes
may be present in a cyst. which also contains sanguineous
and mucopurulent masses. In man. more than 10 flukes
are seldom present in the lungs.
Histologically. the flukes are recognized by the spines
on the surface and by their internal organs (Figs. 45.1 ~
45.3) Typical eggs are present in mature flukes. around
the parasites in the cysts. and in lung tissue outside the
cysts. These eggs usually appear in H&E-stained sections
of paraffin-embedded tissues as double refractile with
polarized Iig ht (Figs. 45.4~45. 7). Eggs of other parasitic
helminths do not show this feature in tissues. a phen-
46. LIVER TREMATODE INFECTION
This is caused by numerous fluke species:
A by Clonorchis sinensis (liver fluke infection).
B by Opisthorchis felineus (cat liver fluke infection) or
Opisthorchis viverrim·1.
C by Dicrocoelium dentriticum (small liver fluke infec-
tion). and
D by Fasciola hepatica (sheep liver fluke infection or
fascioliasis).
A AND B, CHINESE AND CAT LIVER
FLUKE INFECTION
Introduction
These infections are called also clonorchiasis and opis-
thorchiasis. A is closely related to B. practically the only
difference being their occurrence in different geographical
regions. Together they constitute a relatively important
helminthic disease since it is estimated that 20 million
people are infected. 7 million in Thailand alone (0.
viverrini) .
A is found in East Asia. mostly in China. and B in the
temperate zones of Eastern Europe. the former USSR.
India. South East Asia and Japan. Rural populations in
river and lake regions are the main groups affected. men
more than women. It has also been observed in three-
month-old babies.
The definitive hosts are. in addition to man. cats. dogs
and other domestic animals The first intermediate hosts
are water snails and the second intermediate hosts fresh-
water fishes.
Clinically. mild infections may be asymptomatic. In
severe cases. symptoms of the bile duct and gallbladder
with jaundice and cirrhosis may be noted. In chronic
infections. unspecific gastrointestinal symptoms may pre-
vail and carcinomas of liver and pancreas may develop.
163
omen on we are not able to explain. Around the cysts.
and also the eggs. granulomas with giant cells and some
eosinophilic granulocytes may be found.
References
1. Sachs. R. and Kern. P (1982). Epidemiological investigations of
human lung fluke infection in Gabon. Central Africa. VII Intern.
Congr. Inf Paras. Diseases. Stockholm
2. Van Rensburg. I. B. et a/. (1987). Parasitic pneumonia in a dog by
a lung fluke of the genus Paragonimus. J. S. Afr. Vet. Assoc.. 58.
203
3. Duncan. R. B. Jr. et al. (1989). Fatal lungworm infection in an
opossum J. Wild/. Dis .. 25. 266
4. Weina. P. J. and England. D. M. (1990). The American lung fluke.
Paragonimus kellicotti. in a cat model. J. Parasitol.. 76. 568
5. Kraus. A. et al. (1990) Paragonimiasis: an infrequent but treatable
cause of hemoptysis in systemic lupus erythematosus. J. Rheumatol..
17. 244
6. Sachs. R. and Voelker. J. (1982). Human paragonimiasis caused by
Paragonimus uterobilateralis in Liberia and Guinea. West Africa.
Tropenmed Parasit.. 33. 15
7. Miyazaki. I. and Habe. S. (1976). A newly recognized mode of
human infection with the lung fluke. Paragonimus westermani
(Kerbert 1878). J. Parasit. 62. 646
8. Cheng. S. Z. et a/. (1981). Hepatic lesions in 69 children infected
with Paragonimus westermani in Southern Anhui. WHO/Helm. 82.
5
9. Stefanko, S. and Zebrowski, S. (1961). The morphology of cerebral
paragonimiasis. Acta Med Po/., 11, 111
Clinical diagnosis is made by confirmation of the
presence of worm eggs. which are very small. in duodenal
juice and faeces. In serological tests. cross-reactions
with other trematode infections should be taken into
consideration. Ultrasonographic and cholangiographic
methods may be used 2- 6 .
The parasite
The three species, Clonorchis sinensis. also called Opis-
thorchis sinensis or the Chinese liver fluke. Opisthorchis
felineus. the cat liver fluke, and Opisthorchis viverrini can
be distinguished only by minimal details.
The adult flukes are up to 20 mm long and 1.5~5 mm
wide; the Opisthorchis species are a little shorter. They
have a lanceolate leaf-like structure and are almost trans-
parent. Their lifespan is particularly long, up to 25 years
in man (Figs. 46.1 ~46.4).
The eggs of these liver flukes are yellowish-brown, very
small (30Jlm) and jug-shaped (Fig. 46.5).
Miracidium larvae develop from the eggs in the uteri of
mature worms. When they pass out into the bile duct.
they reach (with the bile) the small intestine of the
definitive host and. finally. the faeces. When water is
contaminated by the faeces. the larvae are eaten by water
snails (first intermediate hosts). Inside the snails. they
transform into cercariae. When the cercariae are released
from the snails, they penetrate. through the skin, into
freshwater fish (second intermediate hosts). Within the
fish. they move to the muscles where they transform into
metacercariae.
Pathogenesis
Infection of the definitive host. including man. takes
place by consuming raw fish with metacercariae. These
structures. or young flukes. are released into the small
164 HELM INTHIC DISEASES

Fig. 46.3 Opisthorchis viverrini in the bile duct of a hamster. H&E

Fig. 46.1 Fluke of Clonorchis sinensis. H&E

Fig.46.4 Sucking apparatus of Opisthorchis viverrini. H&E

Fig.46.2 Head of Clonorchis sinensis at higher power. H&E

•
Fig.46.5 Eggs of Opisthorchis viverrini inside the female fluke. H&E
HELMINTHIC DISEASES
intestine, from which they migrate actively into the bile
ducts where they become sexually mature and may lay
eggs. By obstructing the bile ducts and, eventually, also
the pancreatic ducts, these flukes may cause damage
which is different from that caused by other trematodes
in the liver.
Pathology
Practically, only liver, and occasionally the pancreas, may
be Involved. The small worms can be detected with the
naked eye in the bile ducts (Fig. 46.6). The obstruction of
the bile ducts leads to cholangitis, cholangitic abscesses in
the liver tissue, cholecystitis, cholelithiasis and hepatic
fibrosis. I n chronic infections, primary liver carcinomas,
cholangiocarcinoma more frequently than hepatocellular
carcinoma 7.8 may develop (Figs. 46.7-46.11). Pancreas
carcinoma may also be associated with the lesions caused
by this worm infection.
I n contrast to the liver granulomas produced by the
eggs of flukes like Schistosoma and, exceptionally, Para-
gonimus, the lesions in the liver produced by Clonorchis
and Opisthorchis, are caused mostly by mature worms
within the bile ducts and only rarely by eggs (Fig. 46.12).
C, SMALL LIVER FLUKE INFECTION
Introduction
This liver trematode infection is also called 'lancet liver
fluke infection'. Primarily it is a parasitosis of ruminants
and is only occasionally found in man, mainly in children.
Recently, it has been observed in an AIDS patient 9 .
It has been reported in North Africa, Siberia, Turkestan,
South America and West Africa (here the species D.
hospes occu rs instead of D. dentriticum 10).
The definitive principal hosts are sheep and cattle; man
is only an 'accidental' secondary host. The intermediate
hosts are completely different from those of A and B. The
first intermediate hosts are land snails and the second
intermediate hosts are ants.
The parasite
Dicrocoelium dentriticum is also called the small liver
fluke. The adult worms are 5-12 mm long and pale
reddish. The eggs measure 40 JLm and are dark brown.
Development takes place while passing through the
intermediate hosts, see above.
Pathogenesis
Man is infected by inadvertent ingestion of ants. Other-
wise, see A and B.
Pathology
See A and B.
0, SHEEP LIVER FLUKE INFECTION
Introduction
This infection is also called fascioliasis. It is mainly found
in animals (herbivores). In man, infection is observed in
Europe (France, Portugal. Corsica), North and South
Africa, parts of Asia 11 and South America (Brazil. Peru,
Chile).
165
The first intermediate hosts are, again, water snails, and
second intermediate hosts, better described as passive
intermediate carriers, watercress and other aquatic plants.
Cattle, sheep and goats may be used for experimental
studies 12-16
The parasite
Fasciola hepatica is up to 40 mm long and 13 mm broad
(Fig. 46.13). The large oval eggs measure 130-150 x
55-90 JLm, have a small operculum and are yellow-brown
(Figs. 46.14 and 46.15).
The eggs reach water in the same way as those of other
liverflukes. The miracidium larvae hatch out and penetrate
water snails. The cercariae (Fig. 46.16) leave the snails
and attach to various water plants. There they encyst and
become metacercariae.
Pathogenesis
The metacercariae from the ingested aquatic plants, once
in the small intestine of the definitive host penetrate the
intestinal wall and reach the peritoneal cavity. Then, they
penetrate the liver capsule and reach the bile ducts
through the liver parenchyma (Fig. 46.17).
In contrast to the other liver flukes, A, Band C, which
are ascending in the bile ducts, Fasciola hepatica worms,
after maturing in the bile ducts, are descending in these
hollow organs.
Pathology
See A and B. Primary hepatic carcinomas may be observed
in chronic infections.
References
1. Sadun, E. H. (1955). Studies on Opisthorchis viverrini in Thailand.
Am. J. Hyg., 62, 81
2. Bychkov. V. G. et al. (1990). A comparison of the count of
Opisthorchis in the body of the host and of the eggs eliminated
with the faeces. Med. Parazitol. Mosk., 2, 14
3. Pungpak, S. et al. (1989). Ultrasonographic study of the biliary
system in opisthorchiasis patients after treatment with praziquantel.
Southeast Asian J. Trap. Med. Publ. Health, 20, 157
4. AI'perovich. B. I. et al. (1990). Opisthorchis of the liver. Vestn. Khir.,
144.27
5. Dao, A. H. et al. (1991). A case of opisthorchiasis diagnosed by
cholangiography and bile examination. Am. Surg., 57, 206
6. Leung, J. W. et al. (1990). Endoscopic cholangiopancreatography
in hepatic clonorchiasis - a follow-up study. Gastraintest. Endosc.,
36, 360
7. Riganti. M. et al. (1989). Human pathology of Opisthorchis viverrini
infection: a comparison of adults and children. Southeast Asian J.
Trap. Med. Publ. Health. 20, 95
8. Jang, J. J. et al. (1990). Enhancement of dimethylnitrosamine-
induced glutathione S-transferase P-positive hepatic foci by
Clonorchis sinensis infestation in F 344 rats. Cancer Lett., 52, 133
9. Drabick, J. J. et al. (1988). Dicroceliasis (lancet fluke disease) in
an HIV seropositive man. J. Am. Med. Assoc., 259, 567
10. Lucius, R. and Frank, W. (1978). Beitragzur Biologievon Dicrocoel-
ium hospes Loos, 1907 (Trematodes, Dicrocoeliidae). Acta Tropica,
35, 161
11. Kovalenko, V. L. et al. (1990). Fascioliasis of the liver. Arkh. Patol.,
52, 59
12. Santiago, N. and Hillyer, G. V. (1988). Antibody profiles by EITB
and ELISA of cattle and sheep infected with Fasciola hepatica. J.
Parasitol., 74, 810
13. Foreyt. W. J. (1989). Efficacy of triclabendazole against experimen-
tally induced Fascioloides magna infections in sheep. Am. J. Vet.
Res, 50, 431
166 HELMINTHIC DISEASES

Fig.46.6 Two worms of Clonorchis sinensis in the opened bile ducts

near the hilar region of the liver in a 68-year- old patient. Autopsy
material from Japan

Fig. 46.7 Opisthorchis viverrini fluke inside hamster bile duct. Experi-
ment to produce cancer. H&E

Fig.46.8 Same case as Fig. 46.7. Fluke inside bile duct and carcinoma Fig . 46.9 Liver carcinoma (cholangiocarcinoma) produced experi-
on one side. H&E mentally in hamster by Opisthorchis viverrini and co-carcinogen. H&E
HELMINTHIC DISEASES 167

Fig.46.10 Same case as Figs. 46.6-46.8. Cholangiocarcinoma with Fig. 46.11 Same case as Figs. 46.6-46.9. Another field of cholangi-
necrosis. H&E ocarcinoma. H&E

Fig.46.12 Liver granu loma prod uced by eggs of Opisthorchis viverrini. Fig.46.13 Fasciola hepatica fluke. H&E
Same case as Figs. 46.6-46.10. H &E
168 HELMINTHIC DISEASES

Fig.46.14 Fasciola hepatica eggs inside the female fluke. H&E Fig. 46.15 Egg of Fasciola hepatica with operculum in the bile of
cattle. H&E

Fig.46.16 Cercaria of Fasciola hepatica in the water. H&E Fig.46.17 Mature Fasciola hepatica fluke in the bile duct. H&E
HELMINTHIC DISEASES
14. Haroun. E. M. and Hillyer. G. V. (1988). Cross-resistance between
Schistosoma mansoni and Fasciola hepatica in sheep. J. Parasito!..
74. 790
15. Haroun. E. M. et al. (1989). Responses of goats to repeated
47. INTESTINAL FLUKE INFECTIONS
Introduction
The two main intestinal fluke infections are caused by
A Fasci%psis buski and 8 species of Echinostoma.
Infections caused by 5 other species are discussed briefly
at the end of this section.
These trematode infections are of minor importance
epidemiologically. They occur only due to particular
nutritional habits.
A occurs in South East Asia and the Far East1.2. in India.
Bangladesh. Thailand3-5, China and Taiwan, 8 occurs in
India, the Philippines. Celebes and in Brazil.
The definitive hosts in both A and 8 are, in addition to
man, pigs, dogs, cats. monkeys and rodents which act as
animal reservoir hosts. Intermediate hosts in A are fresh
water snails and water plants, and, in 8, water snails,
other snails and mussels. For eXJ)erimental studies of 8,
the golden hamster may be used 6 .
Clinically, infections with A and 8 are similar. Mild
infection is asymptomatic. Severe infection, with hun-
dreds of intestinal flukes, may cause unspecific intestinal
symptoms, like pain and diarrhoea, oedema, ascites,
anaemia and jaundice, and, but only exceptionally, death.
The worms may produce toxic substances.
Clinical diagnosis is easily made by confirmation of
worm eggs, which may be numerous in stools.
The parasite
A, Fasci%psis buski or giant intestinal fluke, also called
Distoma buski, is one of the largest flukes and up to 7 cm
long. Eggs measure 130-40 x 80 p.m.
The miracidium larvae penetrate the body surface of
water snails, become cercariae, and, when again in water,
become attached as metacercariae to water plants.
8, Echinostoma i/ocanum and Echinostoma echinatum or
small intestinal flukes, reach < 1 cm in length, are reddish-
grey and covered by spines (Fig. 47.1). The eggs are
operculated and measure 95 x 65 p.m. The first and
second intermediate hosts are snails and snails or mussels,
respectively.
Pathogenesis
Uncooked water plants or fruits of water nuts with
metacercariae, or raw snails and mussels containing
169
infections with Fasciola gigantica. Vet. Parasitol.. 30. 287
16. Foreyt. W. J. (1990). Domestic sheep as a rare definitive host of
the large American liver fluke Fascioloides magna. J. Parasitol.. 76,
736
metacercariae are ingested and develop into mature
worms. In the bowel they may cause damage by their
numbers.
Pathology
Intestinal flukes are found mainly in the duodenum or
jejunum. or exceptionally, in the large intestine. Superficial
erosion of the intestinal mucosa and hyperaemia of the
small intestinal mucosa may be due to irritation by the
flukes. There is no active tissue invasion by the worms.
Exceptic;>nally, eggs of Echinostoma spp. (8) may be
observed In the CNS and myocardium.
Other intestinal fluke infections
In addition to the Echinostoma infections discussed
above, a few other Echinostoma species may be observed
in man. Furthermore, five intestinal fluke species are
found in man occasionally: Heterophyes heterophyes7 , H.
nocens, Metagonimus yokogawai (Fig. 47.2), Watsonius
watsoni and Gastrodiscoides hominis. They are reported
in countries of East Asia and the Balkans, are small
(1-10 mm long) and their presence in man is usually
symptomless. Their first intermediate hosts are always
snails and their second intermediate hosts may be water
plants or fish.
References
1. Cross. J. H. (1969). Fasciolopsiasis in Southeast Asia and the Far
East: a review. 4th South East Asia Seminar in Parasitology and
Tropical Medicine. Bangkok
2. Buckley. J. J. C. (1939). Observations on Gastrodiscoides hominis
and Fasciolopsis buski in Assam. J. Helminth.. 17. 1
3. Manning. G. S. and Ratanarat. C. (1970). Fasciolopsis buski in
Central Thailand. Am. J. Trap. Med Hyg.. 19. 613
4. Plaut. A. G. et al. (1979). A clinical study of Fasciolopsis buski
infection in Thailand. Trans. R. Soc. Trap. Med Hyg.. 63. 470
5. Sadun. E. H. and Maiphoom. C. (1953). Studies on the epidemiology
of the human intestinal fluke. Fasciolopsis buski (Lankester) in
Central Thailand. Am. J. Trop. Med. Hyg.• 2. 1070
6. Fried. B. et al. (1990). Single and multiple worm infections of
Echinostoma caproni (Trematoda) in the golden hamster. J. Helmin-
thaI.. 64.75
7. Mahmoud. L. H. et al. (1990). A preliminary study of liver functions
in heterophiasis. J. Egypt. Soc. Parasitol.• 20. 83
170 DISORDERS CAUSED BY ARTHROPODS

Fig. 47.1 Echinostoma sp. with anterior sucker. Carmine Fig. 47.2 Metagonimus yokogawai trematode. Carmine
HELMINTHIC DISEASES 171

D. WORM EGGS
Table 18 Nematodes

2 3 q 5 6

3 5

1. Enterobius vermicularis, 55 x 25.um, colourless, ovoid, flattened on 7. Toxocara canis, 75-85.um, not found in human faeces; however,
one side, thick membrane similar eggs of Toxocara cati are found occasionally.
2. Ascaris lumbricoides, 60-70 x 50.um, yellowish, fertile, thick ondu- 8. Gnathostoma spinigerum, 70 x 40.um, yellowish, one-cell stage.
lated outer shell. 9. Capillaria philippinensis, 40 x 20 .urn, flattened, bipolar plug at each
3. Ascaris lumbricoides, infertile. end.
4. Trichuris trichiura, 50 x 25.um, pale to dark brown, two pale polar 10. Dioctophyma renale, 66 x 42 .urn, thick deeply pitted shell, two-cell
prominences. stage.
5. Hookworm, Necator and Ancylostoma are identical, 60 x 40.um, 11. Trichostrongylus sp., 75-100 x 30-50.um, similar to hookworm
glass clear to pale yellowish, 4-cell stage. egg, segmented ovum at morula stage.
6. Strongyloides stercoralis, 55 x 30.um, egg w ith larva, seldom seen
in stools.

Table 19 Cestodes

2 3 5

1. Taenia sp., Taenia saginata and Taenia solium are identical.
32 x 38.um, the outer layer surrounds the yellow-brown radially
striated embryophore around the larva with hooks, in the centre.
2. Diphyllobothrium latum, 50 x 70.um, on one end a lid-like opercu-
lum, on the other, a small knob on the shell. Numerous yolk cells in
addition to the egg cell.
3. Dipylidium caninum, individual egg 25 x 30.um, contains larva with
six hooks, in faeces, found in packets or masses of 30-40 eggs.
4. Hymenolepsis nana, 30 x 50.um, colourless, occurs individually in
faeces, hooks recognizable.
5. Hymenolepis diminutum , 65 x 75.um, hooks are visible.
172 HELMINTHIC DISEASES

Table 20 Trematodes (blood, lung and liver flukes)

3 q 5

6 7
I 9

1. Schistosoma haematobium, 150 x 55 p.m, almost colourless, terminal
spine, only in urine, Schistosoma eggs do not have an operculatum.
2. Schistosoma intercalatum, 140 x 50 p.m, terminal spine.
3. Schistosoma japonicum, 90 x 55 p.m, almost spherical, small lateral
knob.
4. Schistosoma mansoni, 150 x 60 p.m, prominent lateral spine, young
eggs already contain a miracidial larva.
5. Schistosoma mekongi, 40-50 p.m, almost spherical. rudimentary
knobbed lateral spine
6. Paragonimus westermani, 60 x 60 p.m, golden brown, operculum,
initially with 5-10 yolk cells.
7. Clonorchis (Opisthorchis) sinensis, 30 p.m, yellowish-brownish, jug-
shaped, 'lid' at the upper pole.
8. Opisthorchis felineus, 30 x 12 p.m, yellowish-brown, jug-shaped
(collar-like swelling).
9. Dicrocoelium den triticum, 40 p.m, dark brown, contain a fully devel-
oped larva when laid.

Table 21 Trematodes (intestinal flukes)

,
. ~;

3
'-
.
.
I ,
. . :.;.
"r

"

1. Fasciolopsis buski, 130-140 x 80 p.m, eggs of Fasciola hepatica
identical. always numerous in stools, operculate, numerous egg cells
and yolk cells.
2. Echinostoma ilocanum, 65 x 95 p.m, operculate.
5
3. Heterophyes heterophyes, 15 x 25 p.m, operculate.
4. Metagonimus yokogawai, 16 x 28 p.m, operculate.
5. Gastrodiscoides hominis, 160 x 70 p.m, numerous yolk cells.
 Disorders caused by Arthropods
Disorders in this group are common in man and often
very unpleasant. However, in the great majority of cases,
they are not true infections, diseases or parasitoses but
only infestation. They are not normally discussed in the
literature on parasitic diseases. However, to suffer from
infestation of arthropods may be fatal in man.
The principal arthropods, and the disorders or diseases
they produce or transmit are listed summarily in Chapter
I. As ectoparasites, they may: cause allergies, rarely
involving circulatory collapse; act as vectors for viruses,
bacteria and parasites; or serve as intermediate hosts.
Some, however, such as certain insects and mites, may
be completely inocuous and non-parasitic for man.
Table 22 Important arthropods
5 6
1. Pediculus corporis, body or clothing louse.
2. Pediculis capitis. head hair louse.
3. Phthirius pubis, crab louse.
4. Ctenocephalides felis, cat flea
48. SCABIES
Introduction
This skin infection is also called 'the itch' and is produced
by Sarcoptes scabiei or the itch mite. Together with
demodicidosis, it is one of the most frequent ectopara-
sitoses in man. It occurs worldwide, mostly in poor
hygienic conditions and recently, also in patients with
immunodeficiencies1.2, Although it had almost completely
173
IV
Those arthropods which produce epizoonoses may
be pathogenic for man permanently (e.g. lice), tempor-
arily (e.g. blood-sucking mosquitoes) or only accident-
ally (e.g. bees, wasps, etc.). The last situation leads only
to local reactions, pruritus, oedema and pain, as the
consequences of stings or bites. Endozoonoses result
when arthropods (or other micro-organisms) penetrate
the epidermis and remain for a time in the skin of man.
Tables 22 and 23 show the most important arthropods
and diptera (flies and mosquitoes).
The following five disorders are briefly discussed since
some of their features may be of special interest for phys-
icians and pathologists with an interest in morphology.
3 II
7 8
5. Cimex lectularius, bed bug.
6. Sarcoptes scabiei, itch mite, causal agent of the itch.
7. Acarina sp., hard tick, vector of Babesia sp .. etc.
8. Reduviidae sp., assasin bug, vector of Trvpanosoma cruz!.
disappeared after World War II. it is observed again now
and may occur in epidemics 3- 7 It is considered as a kind
of venereal disease and is well known in Venezuela,
Numerous animal species may be infected with varie-
ties of the human Sarcoptes species B These varieties of
itch mite may infect man as a 'false host'. The disease in
man is then named 'animal scabies'
174 DISORDERS CAUSED BY ARTHROPODS

Table 23 Diptera (flies and mosquitos)

2 3

5 6 7 8

1. Nematocera, mosquitos or gnats. The suborder with long antennae
comprises Aedes, Anopheles, Culex, Simulium and Phlebotomus
(Lutzomyia}, transmit numerous diseases.
2. Simulium sp .. black fly.
3. Phlebotomus sp .. sand fly, transmit Leishmaniae.
4. Brachycera, horse fly with the genera Chrysops, Tabanus.
5. Haematoporta pluvialis, rain fly, passive transmission of numerous
bacteria.
6. Glossina sp., tse- tse fly, vector of sleeping sickness.
7. Musca domestica, house fly, passive transmission of numerous
agents.
8. Dermatobia hominis, tropical marble fly, larvae found in myiasis.

Table 24 Life cycle of Sarcoptes scabiei

Stratum corneum

Faeces

------ -----------------------
Mile duel
DISORDERS CAUSED BY ARTHROPODS
Clinically, pruritus, especially in the evenings, is typical.
The intense scratching leads to exanthema and eczema.
Folliculitis, furunculosis and superficial pyodermia may
result in bacterial superinfections, also leading to
glomerulonephritis. In patients with corticosteroid ther-
apy, the lesions became atypical; there may be less
pruritus and explosive reproduction of mites takes place.
Several hundreds of scabies burrows have been found in
this sort of case of infestation. Nodular9- 11 and crusty, or
Norwegian 12- 14 , forms of scabies, already described in the
last century, will be discussed under Pathology. 'Animal
scabies' in man is characterized by rapid healing.
Clinical diagnosis is made by confirmation of the
burrows, the mites themselves or their eggs. Anamnesis
and data about the incubation period lead to suspicion
of this mite infection.
The parasite
Sarcoptes scabiei var. hominis, or the itch mite, belongs
to the subclass acari or mites. They may reach 0.3-0.5 mm
in length, the males being a little shorter than the females.
They have a grey-white ovoid body which is flattened
dorsoventrally and four pairs of short legs. The eggs are
whitish and measure 160-190 x 85-100 f1.m.
The entire developmental cycle occurs in man. For two
months, the female lays 2-4 eggs each day. The larvae
hatch out and develop within 9-10 days to male, or 12-
15 days to female, mites. Outside the host the mites soon
die.
Pathogenesis
Infection takes place from man to man by direct close
contact. The pregnant females of Sarcoptes scabiei reach
the surface of the skin and dig cuniculi or burrows through
the stratum corneum of epidermis, where they lay their
eggs. The incubation period is 4 weeks. Table 24 shows
the life cycle of the mite.
Pathology
With the exception of the back and face, all parts of the
body may be affected (Figs. 48.1-48.4), preferentially,
the interdigital spaces. Commonly, up to 15 mites may
be found in one person. As a consequence of scratching,
exanthema and eczema may be seen. Two other forms
of scabies may be found: nodular and the so-called
Norwegian, or crusty, forms. In the former, firm nodules
with a smooth or scaling surface are found on covered
sites, such as the gluteal and genital regions. Mites are
49. DEMODICIDOSIS
Introduction
Follicle mite infection by Demodex folliculorum and D.
brevis is the most frequent permanent ectoparasitosis in
man. It occurs worldwide, with a high prevalence in older
people. It is called also pityriasis folliculorum.
Man is the exclusive host of these two species of
Demodex. These mites could not be experimentally trans-
mitted into laboratory animals. Ten of the 65 species of
Demodex are pathogenic in man and various domestic
and wild animals 1 .
Clinical symptoms occur rarely. Only massive infections,
with up to 1000 mites in one person, cause skin lesions
and pruritus, almost only on the face. Since the clinical
manifestations are similar to those of rosacea 2- 4 . perioral
dermatitis, granulomatosis, pyodermia and blepharitis 5 ,
the pathogenic role of Demodex infection in these morbid
entities has been discussed, and there are controversial
175
seldom present in the nodular form. The crusty form
is characterized by thick hyperkeratotic papulomatous
plaques.
The mites and eggs (Figs. 48.5-48.8) are located in
burrows, which extend either obliquely or parallel to the
skin surface and reach up to 1 cm long, in the stratum
corneum of epidermis. They do not penetrate the dermis.
Here, a non-specific cellular infiltrate with lymphocytes
and histiocytes is seen, frequently with infiltrates consist-
ing of eosinophilic leukocytes 15 .
In the nodular form, there is a massive infiltrate of
pleomorphic cells with numerous eosinophilic granulo-
cytes. Often, the parasites themselves are no longer found
in this form of the infection. The crusty material in the
Norwegian form of scabies consists of laminar keratin
masses with a sero-fibrinous exudate. It is crossed by
numerous burrows with innumerable mites and eggs.
References
1. Anolik. M. A. and Rudolph, R. I. (1976). Scabies simulating Darier
disease in an immunosuppressed host. Arch. Dermatol" 112, 73
2. Miller. D. A. and Weg. J. G. (1977). Epidemic scabies in respiratory
intensive care unit. Am. Rev. Respir. Dis., 115. 267
3. Shrank. A. B. and Alexander, S. L. (1976). Scabies: another
epidemic? Br. Med. J" 1. 669
4. Barthelmes, R. et al. (1970). Untersuchungen zur Zunahme der
Scabieserkrankung. Dermatol. Monatsschr.. 156. 881
5. Orkin, M. (1971). Resurgence of scabies. J. Am. Med. Assoc., 217,
593
6. Rutli. T. and Mumcuolglu, Y. (1975). Die hiiufigen ubertragbaren
Epizoonosen des Menschen. Gynaekologe. 8. 153
7. Orkin, M. (1975). Today's scabies. J. Am. Med. Assoc., 233, 882
8. Hollanders, W. and Vercruyesse, J. (1990). Sarcoptic mite hypersen-
sitivity: a cause of dermatitis in fattening pigs at slaughter. Vet. Rec"
126. 308
9. Barale, Th. et al. (1971). Nodule post-scabieux. Bull. Soc. Franc.
Dermatol. Syph" 78. 449
10. Marghescu, S. and Ziethen. H. (1968). Ober die nodose Erschein-
ungsform der Scabies. Dermatol. Wschr" 154. 793
11. Thomson. J. et al. (1974). Histology simulating reticulosis in
persistent nodular scabies. Br. J. Dermatol" 421
12. Burks. J. W. et al. (1956). Norwegian scabies. Arch. Dermatol" 74.
131
13. Wishart, S. (1972). Norwegian scabies, a Christchurch epidemic.
Aust. J. Derm" 13. 127
14. Nair, S. R. et al. (1978). Norwegian scabies in Hodgkin's disease.
Swiss Med. Dig. Dermatology. 43
15. Head. E. S. et al. (1990). Sarcoptes scabiei in histopathologic
sections of skin in human scabies. Arch. Dermatol" 126. 1475
opinions about this topic. Corticoids favour the infection
with these mites 6 .7 .
Clinical diagnosis is made by finding mites in the smears
of sebaceous material of hair follicles or sebaceous glands,
as well as in scales or smears of pustular and vesicular
material and the bases of hairs.
The parasite
Two species of mites, also called follicle mites, Demodex
folliculorum and Demodex brevis, are pathogenic for man.
They are morphologically very similar.
The 0.3-0.4mm-long mites are elongated, cigar-like
and have 4 pairs of very short clawed legs (Fig. 49.1).
There is controversy about whether Demodex mites
may passively transmit micro-organisms.
176 DISORDERS CAUSED BY ARTHROPODS

Fig. 48.1 Diffuse scabies in an infant. All gross pictures are patients Fig. 48.2 Scabies in axillary region
from Barinas, Venezuela

Fig. 48.3 'Norwegian form' of scabies Fig. 48.4 Scabies on sale of foot
 DISORDERS CAUSED BY ARTHROPODS 177

Fig. 48.5 Mites of Sarcoptes scabiei in the superior parts of human Fig. 48.6 Mite of Sarcoptes scabiei at higher power in the stratum
epiderm is. H&E corneum of epidermis. H&E

Fig. 48.7 Another mite of Sarcoptes scabiei with visible cuticula. H&E Fig. 48.8 Eggs of Sarcoptes scabiei. photographed with filter
178
Pathogenesis
Infection occurs by direct contact from man to man. The
female Demodex mites are impregnated near the orifice
of the hair follicle ducts. They migrate then into the
sebaceous gland ducts. Demodex fa/lieu/arum mites
remain in the glandular ducts, while the Demadex brevis
mites invade the sebaceous glands themselves. After 12 hours
in?ide the tissues, the females begin to lay eggs. Adult
mites develop, through a larval stage, within 15 days.
Pathology
Mite infections with scarce lesions are commonly found
at sites with numerous sebaceous glands, preferentially
in the face (Fig. 49.2). The nasal region, the zone around
the external auditory canal. the eyelids 8.9 and mamillae
are the most affected sites. Rosacea-I ike and dermatitis-
like lesions with papulo-pustular and vesicular manifes-
tations are noted which may be confused easily with
dermatoses of other origin. The pustules may contain
numerous mites.
Histologically, the Demodex mites are found in the
glandular ducts and in the sebaceous glands (Figs. 49.3-
49.6). In the dermis, perifollicular non-specific cellular
infiltrates are seen. Granulomas have been observed
occasionally, and it is not clear whether the~ are due to
the parasites or to the destroyed hair follicles 1 .11. Electron
microscopic studies have also been performed on this
type of lesion 12 .
50. TUNGIASIS
Introduction
Infection by sandfleas, chigoe or chigger, commonly
limited to the skin of the feet. occurs only in determined
geographical areas, such as Africa, the tropical Americas
and China, mostly in people who walk bare-footed.
Tourists may bring this infection by insects back to their
homelands 1. This very unpleasant infection was well
known in Venezuela when people went around without
shoes. Now it occurs seldom. In Spanish, sandfleas are
called niguas.
In addition to man, this infection is also observed in
pigs, dogs, rats and other mammals.
Clinically, these fleas cause itching lesions, mostly on
the feet. Scratching may lead to secondary infection and
inflammation. Cases of tetanus and gas gangrene are
known due to this flea infection.
Clinical diagnosis is made by squeezing out the lesions
and looking in smears of the liquid for eggs of the fleas.
The parasite
Tunga penetrans is the scientific name for the sandflea,
chigoe or chigger (Fig. 50.1). A synonymous term is
Dermatophi/us penetrans. The fleas belong to the insect
orders, Siphonaptera or Aphaniptera. Nine species of
sandfleas are known 2- 5 .
This is the smallest flea species, reaching only 1 mm in
length and having a reddish-brownish colour. The males
are temporary ectoparasites, while the female fleas are
permanent. remaining in the host until they die. The
ovaries of the females grow to several times their normal
size, reaching the size of a pea. The eggs, when squeezed
out. look like those in Fig. 50.2.
Pathogenesis
Infection occurs when walking bare-footed, either in
houses or shacks or outside in sand or dust. The female
DISORDERS CAUSED BY ARTHROPODS
References
1. Bukva, V. et al. (1988). Pathological process induced by Demodex
sp. (Acari: Demodicidae) in the skin of eland, Taurotragus oryx
(Pallas). Folia Parasitol. Praha, 35, 87
2. Beerman, H. and Stokes, J. (1934). Rosacea complex and Demodex
folliculorum. Arch. Dermatol. Syphilol.. 29, 874
3. Hojyo, 1. and Dominguez, L. (1976). Demodicidosis y dermatitis
rosaceiforme. Med. Cut. I. L. A., 2, 83
4. Rufli, Th .. Mumcuoglu, Y. et al. (1981). Demodex folliuculorum:
Zur Atiopathogenese und Therapie der Rosacea und perioralen
Dermatitis. Dermatologica, 162, 1 2
5. Morgan, R. J. and Coston, T. O. (1964). Demodex blepharitis.
Southern Med. J, 57, 694
6. Weber, G. (1976). Perioral dermatitis, an important side-effect of
Corticosteroids. Dermatologica, 152 (Suppl. 1). 161
7. Ohtaki, N. and Irimajiri, 1. (1977). Demodectic eruption following
the use of topical corticosteroid (in Japanese). Jpn. J Dermatol..
31,465
8. Norn, M. S. (1970). Demodex folliculorum. Incidence and possible
pathogenic role in the human eyelid. Acta Ophthalmol. Suppl.. 108,
1
9. Roth, A. M. (1979). Demodex folliculorum in hair follicles of eye-
lid skin. Ann. Ophthalmo/., 11, 37
10. Seifert, H. W. (1978). Demodex follicularum als Ursache eines
solitiiren tuberkuloiden Granuloms. Z. Hautkr., 53, 540
11. Ramelet. A. A. and Perroulaz, G. (1988). Rosacea: histopathologic
study of 75 cases. Ann. Dermatol. Venereol., 115, 801
12. English, F. P. et al. (1990). Electron microscopic study of acarine
infestation of the eyelid margin. Am. J Ophthalmol., 109, 139
fleas penetrate the skin but the posterior end stays outside
for respiration and laying eggs. The latter transform into
larvae and pupae, becoming adult fleas in 5-6 weeks.
Infestation may occur also when lying naked on the floor
or soil.
Pathology
Skin-penetrating female fleas are found mostly on the
feet. plants, interdigital spaces and beneath the nails.
Only occasionally are other parts of the body affected
(Fig. 50.3-50.5).
Grossly, small hyperkeratotic wart-like foci are found
covered by dark-brown crusts with a central brown-black
dot. Scratching may lead to secondary bacterial infection,
gangrenous inflammation, lymphangitis and tetanus or
clostridial infections. The fleas have been studied ultra-
structurally6.
References
1. Pfister, R. (1977). Nehmen Sandfloh-Infektionen zu? Fonschr. Med.,
95,1373
2. Smith, K. G. V. (1973). Insects and Other Anhropods of Medical
Imponance. The Trustees ofthe British Museum (Nat. Hist.), London,
p. 561
3. Smit. F. G. A. M. (1966). Siphonaptera. In Insecta Helvetica. Impr.
La Concorde, Lausanne, p. 106
4. Rotschild, M. (1965). Fleas. Scientific American, p. 44
5. Cheng, 1. C. (1973). General Parasitology. Academic Press, New
York, London, p. 965
6. Fimiani, M. et al. (1990). Ultrastructural findings in tungiasis. Int. J
Dermatol., 29, 220
 DISORDERS CAUSED BY ARTHROPODS 179

Fig. 49.1 Mite of Demodex folliculorum in dark field Fig. 49.2 Demodecitosis in the face

Fig . 49.3 Demodex folliculorum mites in ducts of sebaceous glands. Fig. 49.4 Mite of Demodex folliculorum in duct of sebaceous gland
H&E at higher magnification. H&E

Fig.49.5 Mite of Demodex cani; in hair follicle. H&E Fig . 49.6 Demodex can;; fragments in hair follicle. H&E
180 DISORDERS CAUSED BY ARTHROPODS

~.
\

I
\ Fig. 50.2 Squeezed out eggs of Tunga penecrans
'.

Fig. 50.1 The sandflea Tunga penecrans

Fig.50.4 Eggs of the sandflea in Fig. 50.3 at higher power. H&E

Fig. 50.5 Horizontal cut of Tunga penetrans. Numerous eggs are

visible inside the sandflea. H &E

Fig. 50.3 Cut sandflea in an interdigital space of the foot. On the left
side and beneath is the necrotic epidermis. The patient. a surgeon from
Munchen. Germany. went around bare-footed while on vacation in
South America. H&E
DISORDERS CAUSED BY ARTHROPODS
51. MYIASIS
Introduction
This entity, also called larval brachycerosis, may be
defined as an infection due to maggots, i.e. larvae of flies
or insects (Diptera) which live on tissues (alive or dead),
in body fluids or in faecal material.
It seems to occur more frequently than commonly
believed, since many cases in industrialized countries,
apparently, are not reported. Distribution is worldwide;
usually infants and old neglected people are affected.
Frequently, the larval infestation befalls sick persons with
chronic lesions. Myiasis is well known in Venezuela 1.
Man is a false host for the larvae of flies. Numerous
domestic animals may be infected by the same insect
species as man 2 .
Clinically, six forms may be distinguished on the basis
of the localization of the larvae in the human body: dermal
myiasis 3- 5 ; wou nd myiasis, 0pthalmomyiasis 6- 11 , cavitary
myiasis 12 , intestinal myiasis 1 and ano-uro-genital myi-
asis 14 ,15. The larvae produce variable symptoms. They may
cause amazement or terror when discovered in the human
body.
Clinical diagnosis is made by recognizing the larvae,
dead or alive.
The parasite
About 80 species of flies (Brachycera or Diptera) , 30 of
them in Europe, may produce larvae which are found in
man. Well-known species are Dermatobia hominis, Musca
domestica, Gasterophilus spp., Hypoderma bovis, Sarco-
phaga camaria and Cordylobia anthropophaga, also
named tumbu fly. Certain species are observed preferen-
tially in distinct geographical areas and in determined
locations or diseases,
The larvae pass through three developmental stages,
and measure from 1 mm up to 4 cm long. Commonly, they
have no head and are segmented (with a head segment).
They are covered by hairs and a whitish-grey colour (Fig.
51.1) .
After the third larval stage, they become pupae and
then adults which may fly and look like 2 cm-Iong bumble-
bees. The developmental cycle from egg to adult fly takes
about 2-3 weeks. Only exceptionally do the larvae grow
into mature adult flies inside the human body, The eggs
measure 1-2 mm. They are laid on dirty clothing, the
floor, plants and, seldom, directly on the skin of man.
Pathogenesis
The portal of entrance for the eggs or larvae of flies are
minor traumata, wounds or ulcers, stings or insect bites
(of all kinds) on skin or mucosae. Once in the tissue, the
larva moves by oral claws and stays alive, growing in
tissues, for variable periods of time. They dig channels
and may then either die or come out by perforation of
skin.
Pathology
Dermal myiasis (synonyms: cutaneous m., dermato m"
subdermal m., aureal m" furuncular m.): The areas of the
head, back (Fig, 51.2) and extremities are mostly involved.
There are three types: furuncular 16 , migratory furuncular
and creeping myiasis. The first begins with a small papule
which itches and grows. The second shows furuncular
swellings in a row, with periodic itching, because the
181
larva moves along subdermally for months, Finally, it
perforates as a mature larva, drops to the floor and
becomes a pupa. The third type, creeping myiasis, is
characterized by a young larva of the first stage, which,
after penetration through skin, moves subdermally in a
tortuous burrow and dies after a while, not reaching
maturity.
The migratory furuncular and creeping myiases must
be differentiated from cutaneous larva migrans or creepi ng
eruption (Section 37).
Wound myiasis (synonym: traumatomyiasis): The
female flies deposit their eggs on wounds or ulcers (Fig.
51,3); larvae being found preferentially in the crusts.
Later, they also attack living tissues, Larvae of Diptera
were or are still used for cleaning necrotic and gangrenous
masses on superinfected ulcerated tumours.
Ophthalmomyiasis (synonym: ocular m.): External
and internal types have been described, The first involves
the conjunctivae, lids, lacrimal glands or periorbital tis-
sues. Commonly, 5-10 small larvae may be found, some-
times up to 50.
The internal type is more dangerous and the conse-
quence of a transcorneal or trans-scleral infestation, The
moving larvae may be visible and cause destructive
irreversible damage and ophthalmitis,
Cavitary myiasis (synonyms: nasopharyngeal m.,
nasal m., pharyngeal m" rhino-pharyngeal m" auricular
m., oral m., oto m.): The synonyms point to the different
locations of the larvae at the facial orifices and cavities,
as well as in the upper respiratory and digestive tract.
Tissues and organs in the vicinity may be involved (Figs.
51.4 and 51.5).
Intestinal myiasis (synonyms: entero m" pseudo m.,
gastro m., intestinal m,): This is the most frequent type of
insect larval involvement in man and the most innocuous,
often asymptomatic. Genuine intestinal myiasis is only
present when migration of larvae occurs from the anus
upwards. Oral infection with larvae, generally present in
the food, is called pseudomyiasis.
The gastrointestinal mucosae are not attacked or
invaded by the larvae. These are later, whether dead or
alive, eliminated with the faeces,
Ano-uro-genital myiasis (synonyms: rectal m., uro-
genital m" bladder m" urethra m.. vulvo-rectal m., vaginal
m., recto-vaginal m.): Again, the above mentioned syn-
onyms point to the anatomical sites involved, Often,
children and old neglected people suffer from this type
of myiasis.
Tissue reaction against the fly larvae is a non-specific
inflammation (Figs, 51.6 and 51.7), Often, bacterial
superinfection with purulent inflammation is present.
Larvae which migrate post-mortem into body orifices and
hollow organs do not evoke an inflammatory reaction.
References
1. Soto, T. S. de and Soto Urribarri, R. (1989). Incidencia de miasis
en pacientes de consulta externa, Kasmera, 17, 31
2. Musa, M. 1. (1989). Observations on Sudanese camel nasal myiasis
caused by the larvae of Cephalopina titillator. Rev. Elev. Med Vet.
Pays. Trap., 42, 27
3. Alexis, J. B. and Mittleman, R. E. (1988). An unusual case of
Phormia regina myiasis of the scalp, Am. J. Clin. Pathal" 90, 734
4. Nderagakura, F. et al. (1989). Myiasis: facial location. Apropos of
a case of Dermatobia hominis infection. Rev. Stomatol. Chir.
Maxillofac., 90, 7
5. Feuerstein, W. et al. (1969). Haut- Myiasis durch Cordylobia anthro-
pophaga, Wiener Klin. Wschr., 81, 634
182 DISORDERS CAUSED BY ARTHROPODS

Fig. 51.1 Larvae of flies which may produce myiasis. Fig. 51.2 Skin lesions of myiasis produced by larvae of Cordy/oba
anthropophaga

Fig. 51 .3 Wound myiasis with numerous larvae Fig. 51.4 Cavitary myasis produced by Sarcophaga camaria larvae
DISORDERS CAUSED BY ARTHROPODS 183

Fig.51.5 Cavitary myiasis of the tonsillar region. H&E Fig . 51 .6 Horizonta l cut of larva of Dermatoba hominis. Note the thick
cuticle. H&E

Fig. 51.7 Pulmonary myiasis. A minimal inflammatory reaction may

be noted around the larva. This means there was an intravital aspiration
of the larva. H & E
184
6. Hatvani. I. (1978). Durch Fliegenlarven verursachte Konjunktivitis.
Klin. Mbl. Augenheilk. 172. 783
7. Feigelson. J. et al. (1976). Un cas de myase oculaire 'Hypoderma
bovis' chez un enfant atteint de mucoviscidose. Pediatrie. 31. 77
8. Loewen. U. (1976). Die Ophthalmomyiasis. Klin. Mbl. Augenheilk..
169.119
9. Zabroda. A. G. et al. (1990). The diagnosis of ophthalmomyiasis.
Oftalmol-Zh.. 2. 126
10. Agarwal. D. C. and Singh. B. (1990). Orbital myiasis - a case report.
Indian J. Ophthalmol.. 38. 187
11. Kearney. M. S. et al. (1991). Ophthalmomyiasis caused by the
reindeer warble fly larva. J. Clin. Pathol.. 44. 276
52. PENTASTOMIASIS
Introduction
This disease is also known as tongue-worm infection
or porocephalosis. Nowadays. this entity is no longer
observed but numerous cases were reported in Europe at
the beginning of this century. It occurred worldwide.
preferentially in tropical countries1.2. the Far East and
Malaysia 3 . In Venezuela. this disease is not known. In
North America. a few cases have been reported 4 .
Man and lower animals may be intermediate or defini-
tive hosts. Natural infection occurs in numerous verte-
brates5. 6 where the tongue-worms are permanent endopa-
rasites or where larvae are harboured in viscera. Several
species of laboratory animals may be used for experimen-
tal studies7 .
Clinically. in man as the intermediate host (infestation
with larvae). rarely abdominal symptoms followed later
by jaundice are noted. In man. as the definitive host. with
worm-like adult parasites in the upper respiratory and
digestive tract. several symptoms may be observed. but
spontaneous cure occurs in 1-2 weeks.
Clinical diagnosis is made by detecting granulomas with
larvae or nymphs in visceral biopsies or by recognition of
worm-like parasites in the upper respiratory tract 8 .
The parasite
The tongue-worms or pentastomids belong to the Penta-
stomidae or Linguatulidae with 60 known species. The
taxonomic position of Pentastomidae is still controversial;
most people consider that this parasite is an arthropod.
Pathogenic to man are. above all. Linguatula serrata (syn.
L. rhinaria) and some species of Armillifer (Porocephalus).
e.g. A. armillatus. A. moniliformis and A. grandii which
were described in the tropics.
The adult parasites are colourless worm-like annelids.
without hairs or legs and a ring-like. but untrue. segmen-
tation. Periorally. flour claws are present. The female
pentastomata are up to 10 cm and the males 2 cm long.
Their lifespan is said to be 2 years.
The larvae are microscopic in size up to 2.5 cm and
have 4 rudimentary legs. The eggs measure 70-90 Jim
(Fig. 52.1).
Numerous eggs are laid by the female and reach the
environment through nasal secretions or faeces. The eggs
ar present in water and on plants. Intermediate hosts.
hares. rabbits and goats (rarely man). become infected
with eggs orally. The eggs become larvae which migrate
through the intestinal wall and reach internal organs via
the bloodstream. When larvae- or nymph-containing meat
is eaten. man and lower animals become definitive hosts
with the adult parasites.
Pathogenesis
Man (and animals) become infested as intermediate hosts
when they consume parasitic eggs with water or unclean
vegetables. The larvae develop from the eggs in the
DISORDERS CAUSED BY ARTHROPODS
12. Sharma. H. (1989). Nasal myiasis: review of 10 years experience.
J Laryngol. Otol. 103. 489
13. Zumpt. F. (1963). The problem of intestinal myiasis in humans. S.
Atr. Med. J. 37, 305
14. Aspoeck. H. et al. (1972). Urethrale Myiasis durch Fannia canicularis
(l). Wiener Kin. Wschr.. 84, 280
15. Aspoeck, H. and leodolter, I. (1970). Vaginale Myiasis durch
Sarcophaga argyrostoma (Rob-Desvoidy). WienerKlin. Wschr.. 82.
518
16. O·Rourke. F. J. (1968). Furuncular myiasis caused by warble fly
(Hypoderma) larvae in patients from County Cork. J Irish Med.
Assoc.. 61. 19
gastrointestinal tract and migrate.' after penetrating the
intestinal wall. into numerous organs. Later. they become
nymphs and produce granulomas.
As the definitive host. man becomes infected by eating
insufficiently cooked meat of rabbits. hares or goats. The
adult parasites grow from the larvae or nymphs and remain
in the region of the upper airways.
Pathology
In man. as intermediate host. the larvae or nymphs may
be found in the intestinal wall. liver. spleen. mesenteral
lymph nodes. kidneys and eyes 9- 14 . The larvae (alive or
dead) are situated in granulomas with necrotic tissue.
which later have thick fibrotic capsules surrounded by
infiltrates of lymphocytes. The granulomas may be similar
to those of larva migrans (Figs. 52.2 and 52.3).
When man is the definitive host. the adult parasites
produce practically no tissue lesions and are soon
expelled.
References
1. Fain, A. and Salvo. G. (1966). Pentastomose humaine produite par
les nymphes d'Armillifer grandis (Hett) au Republique democratique
du Congo. Ann. Soc. BeIge. Med. Trap .. 46. 675
2. Self. J. T. et al. (1975). Pentastomiasis in Africans, a review. Trap.
Geogr. Pathol. 27. 1
3. Prathap, K. et al. (1969). Pentastomiasis: A common finding at
autopsy among Malaysian aborigines. Am. J Trap. Med. Hyg.. 18.
20
4. Guardia. S. N. et al. (1991). Pentastomiasis in Canada. Arch. Path.
Lab. Med.. 115. 515
5. Gill. H. S. et al. (1968). A note on the occurrence of linguatula
serrata (Froehlich, 1789) in domesticated animals. Trans. R. Soc.
Trop. Med. Hyg.. 64. 506
6. Basson. P. A. et al. (1971). Disease conditions of game in South
Africa. Recent miscellaneous findings. Vet. Med. Rev.. 2. 314
7. Boyce. W. M. and Kazacos. E. A. (1991). Histopathology of nymphal
pentastomid infections (Sebekia mississippiensis) in paratenic hosts.
J Parasitol. 77. 104
8. Buslau. M. et al. (1990). Dermatological signs of nasopharyngeal
linguatulosis (Halzoun, Marrara syndrome) - the possible role of
major basic protein. Dermatologica. 181. 327
9. Bouchaert, L. and Fain. A. (1959). Armillifer armillatus infection
with fatal intestinal obstruction. Ann. Soc. BeIge Med. Trap., 39.
393
10. Baird, J. K. (1988). Hepatic granuloma in a man from North America
caused by a nymph of Linguatula serrata. Pathology, 20, 198
11. Gratama. S. and von Thiel, P. H. (1958). Ocular Armillier armillatus
in man. Doc. Med. Geogr. Trop .. 9, 374
12. Rendtorff, R. C. et al. (1962). The occurrence of Linguatula serrata.
a Pentastomid. within the human eye. Am. J Trap. Med. Hyg.. 11.
762
13. Deweese. M. W. et al. (1962). Case report of tongue worm
(linguatula serrata) in the anterior chamber. Arch. Ophthalmol.. 68.
587
14. McKie Reid. A. and Ellis Jones. D. W. (1963). Porocephalus
armillatus farrae presenting in the eye. Br. J Ophthalmol.. 47. 169
 DISORDERS CAUSED BY ARTHROPODS 185

Fig. 52.1 Non-encysted larva of ArmiJIifer armi//atus Fig. 52.2 Dead and calcified larva of Armil/ifer armi//atusin human
tissue. H&E

Fig.52.3 Encysted necrobiotic and degenerated pentastomid larva in

a fibrotic granuloma of the liver. H&E
Index

Italic page references are to figures

Acanthamoeba castallani 52 pathology 119 experimental infection 91

Acanthamoeba albertsoni 52 brain 120. 29.2 gross pathology 91
acanthamoebiasis 49-56 eggs 122.29.13 intestine 92. 18.3
clinical diagnosis 52 experimental inoculation 121. histology 91. 92. 93
differential diagnosis 52. 56 29.7-29.10 exocervix 92. 18.5
epidemiology 49 granulomatous reacting 1 23. intestine 93. 18.6-18.8
experimental infection 49 29.16-29.18 lymph node 92. 18.4
gross pathology 52 intestine 122.29.11. 29.12 parasite 91
histology 53-5 lung 120. 29.3-29.6 cilia 92.18.1.18.2
brain 9.3-9.8 testicle 123. 29.15 pathogenesis 91
Goldner's staining 52.9.2 vasculitis 123. 29.19 Balantidium coli 91
neuronophagy 52. 9.9 Angiostrongylus cantonensis 119 beef tapeworm 144. 147
spinal fluid 53. 9.1 Angiostrongylus costaricensis 11 9 bilharziosis see blood fluke infection
opportunistic infection 52 anisakiasis 11 5-17. 138 black water fever 175
parasite 52 clinical diagnosis 115 black fly 1 31
cytopathic effect 52 epidemiology 115 bladder. carcinoma of the 155
pathogenesis 52 parasite 11 5. 1 16. 27.1 blepharoblast 13. 41
acari 174 pathogenesis 1 1 5 Blastocystis hominis 56. 59
Aedes aegypti 128. 134 pathology 116. 117. 27.2. 27.3 Blastocystis infection 56-9
AIDS 35. 52. 59. 62. 72. 73. 76. 77. 85. 87. Anisakis marina 117 clinical diagnosis 56
95.109.165 anti-Anopheles campaigns 35. 77 differential diagnosis 56
acanthocephaliasis 137 Anopheles 81. 1 28. 134 experimental infection 56
Acanthocephala 1 37 Aphaniptera 178 gross pathology 56. 59
allergic dermatitis 155 Armillifer 184 histology 59. 10.5-10.8
allergic reaction 11. 100. 112. 117. 124. Armillifer armillatus 184 opportunistic infection 59
126. 128 Armillifer grandii 184 parasite 56
Alveococcus see Echinococcus multilocularis Armillifer moniliformis 184 cell block section 57. 10.3. 10.4
Alzheimer nuclei type II 62 arteritis. obstructive in schistosomiasis 155 iron haematoxylin 57. 10.2
amastigotes 13. 15. 18. 23. 27. 29. 35 arthropods. disorders by 173-84 (table 22) signet ring appearance 57. TO.l
amoebae 91 arthropods in man. principal 11 (table 2) pathogenesis 56
amoebiasis 9. 43-9 ascaridiasis 100-4 blindness 116. 126. 128. 131. 138. 147
clinical diagnosis 43 clinical diagnosis 100 blood fluke infection 151-60
epidemiology 43 epidemiology 100 clinical diagnosis 155
gross pathology 43. 46 parasite 100 epidemiology 1 55
chronic intestinal amoebiasis 46 life cycle 100 (table 13) experimental infection 155
hepatic amoebiasis 46.8.10. 8.11. 8.14 pathogenesis 100 gross pathology 155. 157
intestinal amoebiasis 43. 46. 8.3-8.6. pathology 100.101 cercarial dermatitis 157.44.4
8.20.8.21 appendicitis 101 histology 155-9
46. 49.
rare extraintestinal amoebiasis ascaridioma 101 carcinoma of the bladder 158. 44.8.
8.17.8.25 cholangitis 101.103.21.8-21.10 44.9
histology 44-51 intestinal 102. 103.21.1-21.5 cervix 158. 44.7
cervix 50. 8.23. 8.24 liver abcesses 101.103.104.21.6. eggs 156. 44.2
erythrophagia 49. 8.29 21.7.21.11-21.13 intestine. nodular lesion 157. 44.5
intestine 44-51.8.3. 8.7. 8.8. 8.26-8.30 pancreatitis 101 liver granulomas 157. 44.6
liver 47.51.8.12.8.13.8.31 Ascaris 11 lung 158. 159.44.10. 44.11
lung 47.8.16 Ascaris lumbricoides 100. 138 meningo-myelitis 158. 44.12-44.14
lymph node 48. 8.18. 8.19 ascaris roundworm 100 parasite 155. 156. 44.1-44.3
perianal lesion 48. 8.22 Ascaris suum 100 pathogenesis 155
staining 49. 8.2b. c. d asthma 11 5. 138 blood transfusion. babesiosis 69
pathogenesis 43 autoinfection. in strongyloidiasis 109 Bombyx mori 181
X-ray. lung 47.8.15 Brachycera 181
amoebic appendicitis 46 Babesia bigemina 71.74.12.1 brachycerosis. larval 181
amoebic colitis 46 Babesia bovis 69 bradyzoites 59
amoebic dysentery see amoebiasis Babesia divergens 69 brain resembling Swiss cheese 69
amoebic granuloma 46. 49 Babesia microti 69 bronchitis. chronic. in lung fluke
amoeboma 46. 49. 8.9 babesiosis 69-71 infection 160
Ancylostoma braziliense 138 blood transfusion 69 broncho-alveolar lavage (BAL) 85
Ancylostoma caninum 138 clinical diagnosis 69 Brugia malayi 126
Ancylostoma duodenale 106 differential diagnosis 70 Brugia timori 126
anaemia 35. 96. 100. 106 epidemiology 69 buba see leishmaniasis. mucocutaneous
anaemia. hypochromic microcytic 109 parasite 70 buffalo gnats 131
anaemia. iron deficiency type 109. 143 development cycle 70 (table 4) button hole ulcer 43. 8.7. 8.8
anaemia perniciosa 143 maltese cross 70
angiostrongylosis 119-23. 138 pathogenesis 70 Candida 32. 36
american type 119 pathology 70 Capillaria hepatica 1 24. 1 38
asian type 119 blood smear 71. 12.1 Capillaria philippensis 124
clinical diagnosis 119 splenectomy 70 capillariasis 124. 125
epidemiology 119 BAL (broncho-alveolar lavage) 85 clinical diagnosis 124
experimental infection 119 balantidiasis 91-3 epidemiology 1 24
parasite 119. 120.29.1. 29.4 clinical diagnosis 91 parasite 124. 30.2
pathogenesis 1 1 9 epidemiology 91 pathogenesis 124

186
INDEX
187

pathology 124. 125 cytomegaly 62. 87 dwarf threadworm 109

intestine 125. 30..1. 30..3 dysenteric syndrome 43
carcinoma of the bladder 155 Demodex brevis 175 dysentery. amoebic 91
carcinoma of the cervix 41 Demodex canii 179.49.5. 49.6 dysentery. balantidial 91
carp spp. 143 Demodex folliculorum 175. 179
cat liver fluke 163 Demodex spp 17 5 earthworm 100
cercaria 155. 160. 163. 165. 169 demodicidosis 173. 175-8 echinococcosis 141. 145. 148-54
cercarial dermatitis 138. 155. 157 clinical diagnosis 175 clinical diagnosis 148
cestodiasis 141-51 epidemiology 175 serology 148
Chagas disease see trypanosomiasis. parasite 175. 179. 49.1 sonography 148
American pathogenesis 175. 178 X-ray 148
chagoma of inoculation 15 pathology 175 differential diagnosis 148
Cheilospirura spp. 117 face 179.49.2 experimental infection 148
Chiclero ulcer see leishmaniasis. sebaceous glands 49.3. 49.4 epidemiology 148
mucocutaneous hair follicle 49.5. 49.6 gross pathology 151
chigger 178 Dermacentor reticulatus 70 histology 151-4
chigoe 178 dermatitis. cercarial 138. 1 55. 1 57 brood capsule 152. 43.3-43.5
Chinese liver fluke 163 dermatitis. allergic 1 55 foreign body reaction 153. 43.9. 43.10.
cholangiocarcinoma 163 dermatitis. perioral. in demodicidosis 174 scolex 153. 154. 43.6-43.8.
cholangitis 163 Dermatobia hominis 181 43. 11-43. 13
cholelithiasis 163 Dermatophilus penetrans 178 parasite 148. 1 52. 43.1. 43.2
cholecystitis 163 Dicrocoelium dendriticum 163. 165 pathogenesis 1 51
Chrysops 128. 131 Dicrocoelium hospes 165 echinococcosis. alveolaris 148
Ciliophora 91 Dictophyma renale 1 37 Echinococcus 11. 145
clonorchiasis see liver fluke infection dictophymatosis 137 Echinococcus alveolaris see E. multilocularis
Clonorchis sinensis 163. 165 Dienthamoeba fragilis 43 Echinococcus cysticus see E. granulosus
chlorosis 109 Dipetalonema perstans 126 Echinococcus hydaticus see E. granulosus
Cnidosporidia 94 Dipetalonema streptocerca 126 Echinococcus granulosus 148
coccidian spp. 59. 72. 76 diphyllobotriasis 143-5 Echinococcus multilocularis 148. 1 51
Coccidioides immitis 32 clinical diagnosis 143 Echinococcus oligarthus 141
coccidiosis 72 epidemiology 143 Echinococcus patagonicus 141
codworm anisakiasis 11 5 parasite 145. 39.1-39.3 Echinococcus vogeli 141
coenurosis 141 pathogenesis 143 Echinostoma echinatum 169
colitis. balantidial 91 pathology 143. 145 Echinostoma ilocanum 169
colitis. eosinophilic 124 sparganosis 143. 145 Echinostoma spp. 169
complement fixation test. in anisakiasis 115 Spirometra spp. 144. 39.4. 39.5 ectoparasite. general definition 173
conjunctivitis 128 Diphyllobotrium 141 eczema in scabies 174
Cordylobia anthropophaga 181 Diphyllobotrium latum 143 elephantiasis. tropical 126. 128
cor pulmonale. in schistosomiasis 155 Diphyllobotrium pacificum 143 ELISA 134
corticosteroid therapy. scabies 174 Diptera 173. 181 encephalitis. gnathostoma 117
crayfish 160 dipylidiasis 145 Encephalitozoon 94
creeping eruption 106. 109. 138. 181 clinical diagnosis 145 encephalopathy. hepatogenic. in
creeping myiasis 181 epidemiology 145 toxoplasmosis 62
crustaceans 143 parasite 145. 40..1 Endolimax nana 43
crusty form. scabies 175 pathogenesis 145 endometritis. in trichomoniasis 41
Cryptococcus neoformans 26 pathology 145 endozoonosis. general definition 173
cryptosporidians 59 Dipylidium 141 Entamoeba coli 43
cryptosporidiosis 9. 76-8 Dipylidium caninum 145 Entamoeba histolytica 43. 49
AIDS 76.77 Dirofilaria 1 38 enterobiasis 97-100
clinical diagnosis 77 Dirofilaria conjunctivae 1 34 clinical diagnosis 98
epidemiology 76 Dirofilaria immitis 126. 134 epidemiology 97
experimental infection 76 Dirofilaria repens 134 parasite 98. 99.20..1. 20..2
histology 77 dirofilariasis 126. 134-7 eggs 99. 20.2. 20.3
intestine 78. 15.1-15.6 clinical diagnosis 134 pathogenesis 98
parasite 77 epidemiology 134 pathology 98
evolution cycle 76 (table 6) parasite 134. 35.1 appendix 99.20..4
faecal smear 78. 15.1-15.3 pathogenesis 1 34 intestine 99.20.5
Cryptosporidium 77 pathology 134 Enterobius vermicularis 98. 106
cryptozoites 82 Hoeppli-Splendore phenomenon 35.1 Enterocytozoon 94
cucumber tapeworm 145 lung 135.35.2. 35.3. 35.5. 35.7. 35.8 enteritis. eosinophilic. in strongyloidiasis
Culex 1 28. 1 34 pulmonary artery 135. 136. 35.4. 35.6 109
Culicoides 1 26 reservoir hosts 134 eosinophilia 100. 106. 109. 112. 115. 117.
Cyclops 124. 126. 143 Dirofilaria tenuis 1 34 119. 124. 126. 128. 131. 138. 141
cyst. hydatid 148 Distoma buski see Fasciolopsis buski eosinophilia. tropical pulmonary 138
cysticercoid stage 145. 147 distosomiasis. pulmonary see lung fluke eosinophilic infiltrate 101. 106. 124. 138
cysticercosis 141.143.147-50 infections eosinophilic syndrome 128
clinical diagnosis 147 dog heartworm 1 34 epilepsy 116. 138
computed tomography 147 dog tapeworm 145. 148 epizoonosis. general definition 173
immunological methods 147 Donovan bodies 35 erythrophagia. in amoebiasis 119. 8.19
MR (magnetic resonance) 147 double refraction of polarized light. in lung espundia 27
X-ray 149. 42.6 fluke infection 163 exanthema. in scabies 117
epidemiology 147 dracontiasis see dracunculosis exo-autoinfection. strongyloidiasis 109
experimental infection 147 dracunculiasis see dracunculosis eyeworm 128
gross pathology 147. 149. 150 dracunculosis 124-6
brain 148. 149. 42.2-42.5 clinical diagnosis 124 Fasciola hepatica 163. 165
heart 1 50. 42.7 epidemiology 124 fasciolasis see sheep liver fluke infections
histology 148. 150 parasite 1 24. 31. 1 Fasciolopsis buski 169
meninges 150. 42.11 pathogenesis 124 fever. paratoses with fever 11 2
parasite 147.149.42.1.42.11 pathology 126 Fiedler's myocarditis. in American
cysticercus 143. 147 skin 127.31.2 trypanosomiasis 1 5
Cysticercus ce/fulosae 147 Dracunculus medinensis 96 Filaria infections 126-37
Cysticercus bovis 147 dragon worm 124 Filaria. migrating 128
Cysticercus racemosus 148 Durck's granulomas 81 filariasis 126-9
cystitis in schistosomiasis 155 dwarf tapeworm 145. 147 clinical diagnosis 126. 128
 188 INDEX

epidemiology 126 development stage 97 (table 10) clinical diagnosis 138

experimental infections 126 lifespan in man 97 (table 10) epidemiology 137. 138
parasite 128 (table 16). 129.32.1. 32.3 prepatent period 97 (table 10) parasite 138. 139. 37.1
pathogenesis 1 28 source of infection 97 (table 10) pathogenesis 1 38
pathology 128. 129 Hepaticola hepatica 1 24 pathology 138
lymph node 129. 32.4. 32.5 hepatitis granulomatous 124 intestine 140,37.5.37.6
filariasis. human zoonotic 134 hepatitis in amoebiasis 46 liver granuloma 140. 37.7-37.9
filariasis. lymphatic see filariasis hepatosplenomegaly in schistosomiasis 155 myocardium 139.37.2-37.4
flagellates 39. 41 hermaphrodite 96.141.151 larva migrans. cutaneous 106. 138
flagellum 13. 15.41 herring worm disease see anisakiasis larva migrans. visceral 115, 117. 138
flea larvae 145 Heterophyes heterophyes 169 Leishmania 13. 15. 26
flukes see trematodiasis Heterophyes nocens 169 Leishmania braziliensis 27. 29
flukes. paired 155 Hirudo medicinalis 151 Leishmania donovani 29. 35
folliculitis in scabies 174 HIV-l 43 Leishmania donovani chagasi 35
foamy cells 62 Hodgkin's disease and toxoplasmosis 62 Leishmania mexicana 29
fox tapeworm 148 Hoeppli-Splendore phenomenon 136.35.6. Leishmania tropica 27. 29
fungal infection 87 155. 156. 42.2d Leishmania tropica aethiopica 27
furuncular myiasis 181 hookworms 100. 106 Leishmania tropica major 27
furunculosis. in scabies 174 host general definition 9 Leishmania tropica minor 27
hydatid cyst unilocular 151 leishmaniases 9. 13. 26-39
GAE (granulomatous amoebic infection) 49. hydatidosis see echinococcosis leishmaniases. cutaneous 13. 27. 28
52 hydatidosis. secondary 148 anergic disposition 27
gametocytes 80 hydrocephalus. internal 147 clinical diagnosis 27
gamont 70 hydronephrosis in schistosomiasis 155 diffuse type 27
gangrene. in tungiasis 178 Hymenolepsis 141 dry form 27
Gastrodiscoides hominis 169 Hymenolepsis diminuta 145 epidemiology 27
Gastrophilus spp. 181 Hymenolepsis nana 145 gross pathology 27. 28.3.2.3.3
gemistocytic transformation 26. 62 hymenolepsiasis 145-7 histology 27.28.3.4
giant intestinal fluke see intestinal fluke clinical diagnosis 145 humid forms 27
Giardia lamblia 39 epidemiology 145 parasite 27
giardiasis 9. 39-41 experimental infection 145 pathogenesis 27
clinical diagnosis 39 parasite 145.147.41.1 rural type 27
epidemiology 39 pathogenesis 147 urban type 27
histology 39 pathology 147 vector 27. 28. 3.1
faecal smear 40. 6.1 Hypoderma bovis 181 leishmaniasis. cutaneous post-kala-azar 35
intestinal content 40. 6.4. 6.5 hypoproteinaemia. in uncinariasis 106 leishmaniasis. diffuse tegumentary type 29
staining 39 leishmaniasis. mucocutaneous 27-35
parasite 39 ileus. mechanical 101. 119 clinical diagnosis 29
cysts 40. 6.2 ileitis. eosinophilic 119 differential diagnosis 32
trophozoites 40. 6.2. 6.3 immunodeficiency 73. 85, 100. 106. 173 leprosy 32
pathogenesis 3 immunofluorescence. indirect in rhinoscleroma 32
glial cell proliferation 81 dracunculosis 124 histoplasmosis 32
glomerulonephritis in schistosomiasis 155 immunodeficiency 73. 85. 100. 106 diffuse tegumentary type 29. 4.10
glomerulonephritis in scabies 174 immunofluorescent staining in epidemiology 29. 32
Glossina palpalis 23 pneumocystosis 85 gross pathology 29. 32
Glossina morsitans 23 immunological defects 62 ear 30.4.4
Gnathostoma 138 immunosuppression 62. 109. 145 mucosa of the upper respiration tract
Gnathostoma spinigerum 117 infiltration. eosinophilic 11 31,4.11
gnathostomiasis 117. 118 intestinal fluke infection 169-70 nose 29, 30, 4.2, 4.3
clinical diagnosis 117 clinical diagnosis 169 papulomatous lesion 29, 30. 4.5
epidemiology 117 epidemiology 169 skin scar 31, 4.9
experimental infection 117 experimental infection 169 skin ulcer 30. 31,4.6-4.8
parasite 117. 118.28.1. 28.2 parasite 1 69. 170. 47. 1. 47.2 histology 29. 30-4
pathogenesis 117 pathogenesis 169 amastigotes 29. 30. 33, 4.1, 4.12
pathology 117 pathology 169 granulomatous reaction 32. 34. 4.17.
creeping eruption 118. 28.1. 28.3. 28.4 intrauterine infection in cysticercosis 147 4.18
Gongylonema pulchrum 117 Iodamoeba biitschlii 43 Grocotfs method 32
Gram's staining. in microsporidiosis 94 ISHAM congress. June 1991 85 histiocytes 29. 32. 33, 4.13, 4. 14
granulomas. allergic 138 Isospora belli 59. 63. 76 kinetoplast 29
granuloma. eosinophilic 128. 131. 138. 155 Isospora hominis 73 lymphadenitis, regional 32
granuloma of Durck 81 isosporosis 59. 73. 75. 76 phagocytosis 32. 33, 4.15
granuloma of the liver in schistosomiasis AIDS 73 tissue reaction 34, 4.16. 4.19
155 clinical diagnosis 73 parasite 29. 4.12
granuloma of the liver in liver fluke epidemiology 73 parasitaemia 29
infections 163 parasite 73 pathogenesis 29
granulomatosis in demodicidosis 175 faecal smear 75.14.1-14.3 leishmaniasis of the Old World see
granulomatous reaction 11.87.119, 124. pathogenesis 75. 76 leishmaniasis, cutaneous
143. 163. 184 pathology 76 leishmaniasis of the New World see
green sickness 109 itch mite see scabies leishmaniasis. mucocutaneous
Grocott's method 85. 87. 94 Ixodidae 70 leishmaniasis, visceral 35-9
ground itch 106 Ixodes ricinus 70 AIDS 35
Guinea worm 124 clinical diagnosis 35
gynaecophoric canal 155 jaundice. in pentastomiasis 184 differential diagnosis 35
gross pathology 35
haematin see malaria pigment kala-azar see leishmaniasis. visceral histology 35-8
Haemoflagellate infections 13-26 kinetoplast 13. 15. 23. 29. 35. 62 liver 36. 38. 5.2. 5.9-5.11
haemolysis. intravasal. in malaria 81 lymph node 36. 37. 5.3-5.6. 5.12
haemoptysis, endemic. in lung fluke lagoch i lascariasis 1 37 Russell bodies 35. 38. 5.12
infection 160 Lagochilascaris minor 1 37 small intestine 37. 5.7, 5.8
haemorrhages. annular. in malaria 81 lancet liver fluke 165 spleen 38, 5.13
Haemosporidia 80 larvae. ciliate 143 parasite 35
haemozoin see malaria pigment larvae of pork tapeworm 147 kinetoplast 35
Haplosporidia 85 larval stage 147. 151 promastigote 35
helminthic diseases 96-172 larva migrans 100. 126. 128. 137-41 pathogenesis 35
INDEX 189

leishmanioma 35 kidney 84, 16.12 Naegleri 49, 52

lice, dog hair 145 liver 83,16.10 Naegleri australiensis 52
Lieberkuhn's crypts 112 placenta 83, 16.9 Naegleri fowleri 52
LM see larva migrans parasite 80, 81 Necator american us 106
Linguatula rhinaria 1 84 gametocytes 81, 16.1 necatoriasis see uncinariasis
Linguatula serrata 1 84 intraerythrocytic structure 79 (table 7) Nemathelminthes see nematodiasis
Linguatulidae 1 84 trophozoites 81, 16.1 nematodiases, rare and uncommon 137
linitis plastica, in strongyloidiasis 109 schizonts 81,16.1.16.2 nematodiasis 96-141
lipoproteinosis and pneumocystosis 87 pathogenesis 81 anatomical features 97.98 (tables 11, 12)
liver carcinoma, primary, in liver fluke evolutionary cycle 80 (table 8) evolutionary cycles 96, 97
infection 163 malaria, bovine 69 ascaris type 96
liver fluke infection, chinese and cat 163-7 malaria, cerebral 81 enterobius type 96
clinical diagnosis 163 malaria, congenital 81 hookworm type 96
epidemiology 163 malaria, imported 77 trichinella type 97
parasite 163, 164, 46.1, 46.2, 46.4, 46.5 malaria, malignant 77 nephrosis, haemoglobinuric, in malaria 81
pathogenesis 163, 165 malaria, pernicious 77 neurocysticercosis 147
pathology 165 malaria pigment 81, 83 ngana 23
bile duct (hamster) 164,46.3, 46.7 malaria tropica 77 niguas 178
bile duct (man) 164, 46.6 malabsorption syndrome, in strongyloidiasis NNN medium 15, 26, 52
cholangiocarcinoma (hamster) 109 nodular form, scabies 175
46.8-46.11 maltese cross, in babesiosis 70 Norwegian form, scabies 175
liver granuloma 164, 167,46.12 mango fly 128 Nosema 94
liver fluke infection, small 165 Mansonella ozzardi 126 Nosema connori 94
AIDS 165 Mansonia 128 nosematosis see microsporidiosis
epidemiology 165 Medina worm 124
oesophageal bleeding, in schistosomiasis
parasite 165 mega~organs, in American trypanosomiasis
155
pathogenesis 165 18
oesophagostomiasis 137
pathology 165 Meleney's synergistic gangrene, in
Oesophagostomum 106, 137
liver fluke infection, sheep 165-9 amoebiasis 46
Onchocerca armillata 131
clinical diagnosis 165 meningoencephalitis, eosinophilic, in
Onchocerca caecutiens 131
epidemiology 165 angiostrongylosis 119
Onchocerca volvulus 126
experimental infection 165 meningo~encephalomyelitis, in
onchocerciasis 126, 131-4
parasite 165, 168. 46.13 micronemiasis 137
clinical diagnosis 131
cercaria 168, 46.16 merozoites 72, 73, 81
epidemiology 131
eggs 168, 46.14 Mesocestoides spp. 141
gross pathology 131
pathogenesis 165 metacercaria 160, 163, 165, 169
onchocercoma 131
pathology 165 Metagonimus vokogawi 169, 47.2
histology 131
bile (cattle) 168,46.75 metastasis formation, in echinococcosis 151
skin lesion 132, 133, 34.2, 34.3,
bile duct 168, 46.17 Metazoa 96
34.6-34.8
liver glia 62 Meyers-Koumenaar syndrome 138
parasite 131, 132, 34.1,34.4,34.5
liver granuloma, in schistosomiasis 155 Microfilaria bolivariensis 126
pathogenesis 131
liver trematode infection 163-9 microfilaria, scheme of 126 (table 15)
Onchocercoma 131
Loa loa 126, 128 Micronema deletrix 137
oocysts 72, 76
loa worm 128 micronemiasis 137
operculum 143, 160, 165
loiasis 128-31 M icrospora 94
ophthalmitis, granulomatous, in larva
clinical diagnosis 128 Microsporidia 85
migrans 138
epidemiology 128 microsporidiosis 94, 95
opistorchiasis see liver fluke infection
parasite 130,33.1, 33.2 AIDS 94
Opisthorchis felineus 163, 165
pathogenesis 131 clinical diagnosis 94
Opisthorchis sinensis 163
pathology 131 differential diagnosis 94
Opisthorchis viverrini 163
Laffler's syndrome 100, 101, 138 experimental infection 94
opportunistic infection 52, 59, 76, 85, 95,
lung trematode infection 160-3 histology 94, 95
97
clinical diagnosis 160 gastric carcinoma 95, 19.5, 19.6
ovoviviparous 128
differential diagnosis 160 halo 94, 95, 19.2
oxyuriasis see enterobiasis
epidemiology 160 muscle 95, 19.1, 19.3, 19.4
Oxyuris vermicularis 98
experimental infection 160 parasite 94
parasite 160 pathogenesis 94 Papanicolaou staining 41, 46
pathogenesis 160, 163 Miescher's tubules 72 Pappenheimer bodies 70
pathology 163 miracidium 155, 160, 163. 165 paludism see malaria
eggs and granulation tissue 161,45.4. miscarriage 62, 81 PAM E (primary amoebic meningo~
45.6 Moniliformis moniliformis 137 encephalitis) 49, 52
eggs in polarized light 162, 45.7 mononucleosis, in toxoplasmosis 62 pancreas carcinoma, in liver trematode
pulmonary cyst 161, 45.1, 45.2, 45.3. Montenegro skin test 27, 29 infection 163. 165
45.5 Morerastrongvlus costaricensis 119 Paracoccidioides brasiliensis 32
Lutzomyia 35 morula cell 25, 2.6, 2.8, 2.9 paragonimiasis see liver fluke infection
Lutzomvia longipalpis 29 Mott bodies 25,2.6,2.8,2.9, 26 Paragonimus 160
Iympadenitis, eosinophilic 111, 129, MR (magnetic resonance) 147 Paragonimus africanus 1 60
24.10-24.12,32.5 Musca domestica 181 Paragonimus kellicotti 160
lymphadenitis, Piringer-Kuchinka 62 mussels 169 Paragonimus westermanni 1 60
MVcobacterium tuberculosis 85 Parastrongvlus cantonensis 11 9
Macracanthorhvncus hirudinaceus 137 myiasis 138, 181-4 Penicillium marneffi 32
macrofilariae 126 clinical diagnosis 181 pentastomiasis 184, 185
maggots 181 epidemiology 181 clinical diagnosis 184
malaria 9, 70, 77-85 parasite 181 epidemiology 184
clinical diagnosis 79 larvae 182, 51.1, 51.6 parasite 184
epidemiology 77 pathogenesis 181 larva 185, 52.1, 52.2
experimental infection 77 pathology 181 pathogenesis 184
gross pathology 81 cavitary myiasis 182, 183,51.4,51.5 pathology 184
bone marrow 83, 16.6 pulmonary myiasis 183, 51.7 granuloma of the liver 185, 52.3
brain 83, 16.7 skin 182,51.2 Pentastomidae 184
kidney 82, 16.5 wound myiasis 182,51.3 perforation, intestinal. in ascaridiasis 101
spleen 83, 16.4 myocardial degneration, fatty, in uncinariasis periodicity, day and night in loiasis 128
histology 81-4 109 peritonitis, granulomatous, in ascaridiasis
brain 83, 84, 16.8, 16.11 101
190 INDEX

Phlebotomus 27. 29.3.1. 35 Sarcocystis lindemanni 72 Taenia 141

Phlebotomus panamensis 29 Sarcocystis spp. 94 Taenia cysticercus 148
pian bois see leishmaniasis. mucocutaneous Sarcocystis suicanis 73 Taenia mUlticeps 141
pinworm infection see enterobiasis Sarcocystis suihominis 59. 72. 73 taeniasis 141-3
pipe stem fibrosis. in schistosomiasis 155 Sarcophaga canaria 181 clinical diagnosis 141
Piringer-Kuchinka lymphadenitis. in Sarcoptes scabiei var hominis 173. 174. 175 epidemiology 141
toxoplasmosis 62 (table 24) parasite 141.143.38.1-38.5
Piroplasmia 70 Sarcoptes spp. 173 pathology 143
piroplasmosis 69 sarcosporidiosis 59. 72-4 Taenia saginata 141
pityriasis folliculorum see demodicidosis clinical diagnosis 72 Taeniasolium 9.141.147
Plasmodium 77. 79. 81 differential diagnosis 72 Taenia teniforme 141
Plasmodium berghei 77 epidemiology 72 tapeworm infection see cestodiasis
Plasmodium brazilianum 77 gross pathology 72 tertiana type of malaria 79
Plasmodium cynomolgi 77 histology 72. 74 tetanus in tungiasis 174
Plasmodium knowlesi 77 intestine 74. 13.3-13.6 Theileria spp. 69
Plasmodium malariae 77.80 myocardium 74.13.1 Thelazia callipeda 117
Plasmodium ovale 77.80 oesophagus 74. 13.2 Thelohania 94
Plasmodium vivax 77.80 parasite 72 threadworms see nematodiasis
plerocercoids 143 development cycle 73 (table 5) ticks 69. 70
Plysaloptera caucasica 117 pathogenesis 72 toluene blue staining 98
PMS (phagocytic-mononuclear-system) 35. scabies 173-175 toluidine blue method 85. 87
81 clinical diagnosis 175 tongue worm 184
Pneumocystis carinii 62. 85 epidemiology 173. 174 Torulopsis glabrata 32
pneumocystosis 9. 85-90 parasite 174 (table 24). 175. 176. Toxocara 1 38
AIDS 85 48.5-48.7 Toxocara canis 116
clinical diagnosis 85 eggs 177.48.8 Toxocara cati 116
epidemiology 85 pathogenesis 175 toxocariasis 11 5. 116
experimental infection 85 pathology 175.176.48.1-48.4 clinical diagnosis 115
extrapulmonary lesions 85 Schistosoma 151. 155 epidemiology 11 5
gross pathology 85. 87 Schistosoma curassoni 1 55 parasite 115. 26.1. 26.2
pneumocystoma 86. 17.5 Schistosoma haematobium 151. 155 pathogenesis 11 5
histology 87-90 Schistosoma intercalatum 151. 155 Toxoplasma gondii 32.59.61.62.94
alveolar content 88. 89. 17.10-17.13. Schistosoma japQnicum 151. 155 toxoplasmosis 9. 59-69. 72
17.15 Schistosoma mansoni 151. 155 AIDS 59.62
granulomatous reaction 90. Schistosoma mekongi 151. 155 clinical diagnosis 59
17.16-17.21 schistosomes 1 51 differential diagnosis 62
liver 86. 17.4 schistosomiasis see blood fluke infections epidemiology 59
lung 86.88.17.1-17.3.17.7 schizont 70. 80 experimental infection 59
lymph node 88. 17.6 SchOffner's dots 80 extrauterine infection 59. 61. 62
parasite 85.88. 17.8-17.9 scolex 141.143.145.148.151.153 gross pathology 62. 65. 66. 68
pathogenesis 85 sheep liver fluke 163 lymphadenitis 62
pneumonia. pneumocystis 85 shock. anaphylilctic. in echinococcosis 148 medulla oblongata 65. 11.22
pneumonia. interstitial plasma cell. in Simulium flies 131 ophthalmitis 62.64.11.11-11.13
pneumocystosis 85 Siphonaptera 178 histology 60. 63. 63-8
pneumonia. eosinophilic. in dirofilariasis 134 skin test 115. 124. 128 bone marrow smear 60. 11.1
porocephalosis see pentastomiasis sleeping disease 9 chorioretinitis. ophthalmitis 60. 62. 63.
pork tapeworm 141. 147 sleeping sickness see African trypanosomiasis 64. 11.7-11.13
portal hypertension. in schistosomiasis 155 small liver flukes 163 cysts 60.62.65.11.3-11.5.11.16
prepatent period 96. 97 (table 10) snails 163. 169 encephalopathy 62. 65-7. 11.23-11.32
proglottids 141. 143. 145. 148 soil amoeba see acanthamoebiasis lung 64.65.11.16.11.17
promastigote 29 sore of Aleppo. Biskra. Delhi. Jericho see muscle 65.11.19
pseudocysts 59. 62 leishmaniasis. cutaneous myocardium 64.11.14.11.15
Pseudoterranova decipiens 117 sore. oriental see leishmaniasis. cutaneous orchitis 65. 11.20. 21
pseudotumor. parasitic. in lung trematode Spargana 143 pleural exudate 60. 65. 11.2. 11.18
infection 160 sparganosis 138. 141. 143 intrauterine infection 59. 61. 62
pulmonary hypertension. in schistosomiasis Sparganum proliferum 141 hydrocephalus 68. 11.38-11.39
155 spiruids 117 miscarriage 62
pyelonephritis. in schistosomiasis 155 Spirometra spp. 138. 141. 144. 39.4. 39.5 placentitis 62. 68. 11.33-11.37
pyodermia. in scabies 175 splenomegaly. in leishmaniasis 35 opportunistic infection 59. 62
pyrexia. in larva migrans 138 sporocysts 72. 73 parasite 59. 61
sporulation 59 evolutionary cycle 61 (table 3)
quartana type of malaria 79 Sporothrix schenckii 32 sickle shaped feature 59.60.11.1-11.3
Sporozoa 59. 70. 76. 80. 85 pathogenesis 59. 61
rat tapeworm 147 sporozoites 76. 85 serology 59. 62
Reduviidae 23 status spongiosus 62 TPE (tropical pulmonary eosinophilia) 138
refraction. double 81 stool specimens. handling of 106 transmission. general definition 11
renal insufficiency. in malaria 81 Strongyloides 138 trematode spp. 1 51
retinal detachment 116. 138 Strongyloides stercoralis 96. 109 trematodiasis 151-69
retroinfection. in Taenia solium 147 strongyloidiasis 9.97.109-12 Triatoma 23. 1.8
rhabditiform 96. 101. 110 AIDS 109 Trichinella pseudospiralis 112
rheumatic pain. in cysticercosis 147 clinical diagnosis 109 Trichinella spiralis 112
rhodamine staining 85. 87 epidemiology 109 Trichinella spp. 124
Rhodnius prolixus 16. 1.8 gross pathology 109 trichinellosis see trichinosis
river blindness 131 histology 109-111 trichinosis 112-15
Romana sign 15. 16. 1.9 colitis 111. 24.7 clinical diagnosis 112
rosacea. in demodicidosis 175 gastric ulcer 110. 24.2 epidemiology 112
rostellum 145 lung 111. 24.8. 24.9 experimental infection 112
round worms see nematodiasis lymph node 111. 24.10-24.12 parasite 112. 113. 25.1. 25.2
Russell bodies 26. 35 intestine 110. 24.3-24.6 pathogenesis 11 2
suction disk 39 pathology 112-114
sandfleas 178 swamp fever see malaria intestine 113. 25.3
saprophyte 62. 85 swimmer's itch 138 musculature 114. 25.4-25.8
Sarcocystis bovifelis 72 Trichocephalus trichuris 101
Sarcocystis bovihominis 59. 72. 73 tachyzoites 56 Trichomonas 11
INDEX 191

Trichomonas vaginalis 41 inoculation chancre 23. 24. 2.4 ulcer. tropical see leishmaniasis. cutaneous
trichomoniasis 41-3 parasite 23 uncinariasis 101. 106-9
clinical diagnosis 41 pathogenesis 23 clinical diagnosis 106
cytology 41.42.7.1.7.2.7.4 pathology 23 epidemiology 106
epidemiology 41 vector 23. 24. 2.3 experimental infection 106
histology 41. 42 trypanosomiasis. American 13-22 gross pathology 106
endocervix 42. 7.5. 7.6 clinical diagnosis 13 intestine 107. 23.6
pathogenesis 41 Romaiia sign 16. 1.9 myocardium. fatty degeneration 108.
trichostrongyliasis 137 xenodiagnosis 13 23.9
Trichostrongylus 106. 137 X-ray 16. 1.11 histology 109
trichuriasis 101. 105 epidemiology 13 intestine 108. 23.7. 23.8
clinical diagnostic 101 gross pathology 1 5. 18 parasite 106
epidemiology 101 heart 17.1.13-1.16 life cycle 106 (table 14)
experimental infection 101 histology 15. 18-22 worm 107.23.1-23.5
parasite 101. 105. 22.1. 22.2 blood smear 14. 1.4-1.5 pathogenesis 106
pathogenesis 101 central nervous system 16. 19. 20. 1.7. urolithiasis. in schistosomiasis 155
pathology 101 1.19-1.23 uta see leishmaniasis. mucocutaneous
appendix 105. 22.4 intestine 20. 1.25. 1.26. 1.28
caecum 105. 22.3 mediastinum 14. 1.2 vector. biological. general definition 11
Trichuris trichuria 101. 106 myocardium 15.18.21.22.1.1.1.6. Virchow-Robins spaces 18
Trichuris vulpis 138 1.10.1.12.1.17.1.18.1.30-1.35 volvulus. in ascariasis 101
trophozoites 39. 70. 72. 81. 91 oesophagus 20. 2.4
tropism of cysticercosis 147. 148 orchitis 21. 1.29 water amoeba see acanthamoebae
trypanomastigotes 13. 15. 23. 26 placenta 20. 1.27 water snail fever see blood fluke infection
Trypanosoma brucei 23 tongue 14. 1.3 water cress 165
Trypanosoma brucei brucei 23 parasite 13 waterplants 165. 169
Trypanosoma brucei gambiense 23. 24. 2.2 pathogenesis 15 waternuts 169
Trypanosoma brucei rhodesiense 23. 24.2.1 vector 1 5. 16. 1.8 Watsonius watsoni 169
Trypanosoma cruzi 13. 15. 26. 29. 32. 94 tsetse fly 23. 24. 2.3 Whipple disease 62
Trypanosoma rangeli 13. 15. 1.5 Tunga penetrans 178 whipworms 100
trypanosomiasis. African 23-6 tungiasis 178. 180 whipworm infection see trichuriasis
clinical diagnosis 23 clinical diagnosis 178 worm eggs 171. 172 (tables 18-21)
epidemiology 23 epidemiology 178 Wucheria bancrofti 126
histology 23. 24. 25 parasite 178. 180. 50.1. 50.5
blood smear 24. 2.2 eggs 180. 50.2 xenodiagnosis. general definition 13
choroid plexus (mouse) 24. 2.1 pathogenesis 178
encephalitis 25. 2.5. 2.7 pathology 178 Ziehl-Neelsen method. in crytosporidiasis
morula cell 25. 2.6. 2.8. 2.9 interdigital space 180. 50.3. 50.4 77